Council for Tobacco Research
Advances in Modern Toxicology New Concepts in Safety Evaluation [St Syrian Hamsters Are A Valuable Option for Animal Experiments]
Abstract
MIS;ILL
Fields
- Master ID
- Ctrmn00041967-2810
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- Author
- Hemisphere Publishers
- Blumenthal, H., Fda
- Homburger, F., Bioresearch Inst
- Mehlman, M.A., Nih
- Shapiro, R.E., Natl Inst For Environmental Health
- Blumenthal, H., Fda
- Depository Date
- 08 Sep 1997
- Box
- 267
- Type
- SCIENTIFIC ARTICLE
- UCSF Legacy ID
- bot30a00
Document Images
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Advances in Modern Toxicology
, VOLUME 1, PART 1:
P,
NEW CONCEPTS
IN SAFETY EVALUATION
EDITED BY
MYR0NA. NfEHL%14`
\,kTIOI%AL 1NSTITL'TES OF HEALTH
RAYMOND E. SHAPIRO
M'1T1TE OF E%NIRO%,HE%TAL N.EALTH SCIENCES
HERBERT BLl,*\1E~THkL
F(DG:> >ND DR,G >D%!.\IiTRaT;O`
E
HEMISPHERE
PUBLISHING CORPORATION
W3shington London
'A HALSTED PRESS BOOK
JOHN WILEY & SONS
New York London Sydney
! )it
Torontu
EXHIBIT NO: L
N:T1 CE
This r, ='i''3f TaY :e
awt,^;eo OY Co;Yn~,t
(T~tl2 il u.5. COWt).
CTR NN 042627
I
t
CONTENTS
i
i
De1:i:tr,;n %
PP:' e r~,
L, . Frxcir-.Jn-.a Bp:e! B.gi~, :: vt
PART I INTER>CTIO\S I
CHAPTER ' Rnle of Interactn,n of Enwonment3l >gents in \1ud,f.tng
Their k3to!u_£i:3l a,tn!t% '.r.i ~, 3
T: \ 3
R: .rc^.:s ti
CHa?TER :
\tudcrn Cun;epts in Nutr:ttonzl Status and Fore:gn Compound
Tu.::,r.. TL* ..+ CJ-^,^tc!! I I
Fxe-¢:+ Co^.puunJ
\!e'~^,i ~^.i 1:
In%..;.:r.z Farr:,;, Cun-.counJ \te:113ousm IS
\t.. ~~. ^:\t..c. F.n,',,.n U%'ast k%~,nu S~ i,em I S
1t
Re;.,mmended Protu~uls iur S:uJ,cs ui Nwr,.ttun-Fore:¢n
C: rrround In!eru,uuns 21
Re:e:cnces :4
PART 11 CO%,CEPTI,'Al..1%D \tETHODOLOGICAL TOOLS 31
CHAPTER : Potential Contnbution of Inbred S%run H=sters to Future
Tu.rcolo¢v F llurDurger 35
35
S;e::,,: Chjra;ter,set,s ut H3msters 37
I :h :J L,nes .:I H,,rr.stvs 34
S;e.:ii l ses 2! Pe.,a,,r Inb:e : Hamster Susccpt;ti!tttes
S:!'e!. Tcst:re vi C eiret!c Smu:e 43
S.,.:~ n !hc Tj:t 45
u
43
Cf R MN 042622 8
/j
I
I
% ur
Stud:es on Su5:ut3neoUi SY.:I.^1 l.'. ....... .t i.. .. ~J1."i
o: S~rlla H3msters 46
SlJd:es on Indu;tion .f C.,,%... .. ~e L:... . 3..__.
Harnsters 46
St -iJies on the ii Re^~: :sins +n S. -.ar.
Hamsters 47
In,;rJcn:e of Spwntane,ius N,:o;:jsmsm S~::j:t Hlr.is;c:s 4'
App+it.auoit of the Abone Obier%3uuni w Sjiet~,
E%jlujtwns 49
Epilogue SI
Reicrcr.cts 51
1
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1
r
CHAPTER; Concepts in Health E%rluatiun uf Commer:tat and i:,du'tna!
Chemicals. B. P ti1c AJr>Jr1 61
(.,on¢Term %ersus Short-Term Tov:!t% Tests ol
Lepl Requirements for S3tet.
C`urii::als 61
Tini! RcquIred :u De ~r.,,.... \ ,.t ... ~ ...
Te;t .,;3i Inimmatta^ on t.a;tig-Te. -,ecs,;s S, :.
Ttitiaz ob
@3.i.:.~~nJ 66
sseil jnd !s!e n::j bb
Opinion from 0t,;c: b-
Elra S.cns jnJ T: s..: C
.. ~ _ .
Tcr:n \,Eiil;t 3-JI t.un._T:rn %..E.::;: 0 .:s "I
Repr~~ S5
S aes:ed
Tes:in¢ 96
Ger.e:al 96
C3r: ~;gen~:::} 10:
Rc~r~Ju::.~n l0:
Summary 103
References 104
appen3tx Data *r.,,, Snvc:Te:ni a-._ .. _Tr'^- :
Obt3rned fro:n %'3nous Ute:vutt S...:::: 1 to
References 136
.... .....
i
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,
wk
Conlenrt ix
CHAPTER 5 Assessment of the Value of Sy stemic Toaicitv Studies in
Experimental 4nimals. Tihvr &aa:s 141
Intr,)Ju:u,~n 141
Prospectrve S:udres
141
L:mitations 142
LD:O Drtermi.^..,:;ors 145
Tes:s 1-16
.,
R: . ,..;es 140
I
CHAPTER 5 Current Methodolop in Tento!oe% Rewarch
; . :: F V : : ,s . .: ! C .. :s
;!: ~^, ! ~5
n- :. ~es 15"
Er c.~:~.~::s ISS
100
F ., ... ('_.. . _ T.-. Ie3
F_. T:.. ,.. 164
N' .._ s It+tt
155
C`~ % PTER ' \on!erha! P3r3meters» Indices of Acute Toucrtv Inadequaev
of the >cute LD50 F,eJrr,cr
T: %; 1".
R;:erences 1Q9
P\RT III PH>RNACOKIN'ETICS A `EW TOOL 193
CNkPTER S Pharmaeokinetic Studies in Esaluation of the Toticological
and En.rronment3I Hatard of Chemicals.
P J GehnnS. P G. Isbran2be. jr;,; G E BlJu 195
b.tsic Cjn;eprs in Phv macoktnetres 196
Introdu;uwn 196
C)-.e C.:rnp.rtmert Open Mode! 198
TwJ-C_npJCtment k1u!u;omp3rtm.ett Open Model
S' S:tTS :05
Retvuted AJrrints:rvron or Repeated Et;esure :08
tanetics of Non,tnev or Svur,^!e Sss;er,s :11
C,%vent Bi.^.!:::e :j %1jcr,)rro!e;u!e) t Pr,i:e:n. DN A. and
RN al 215
/1
~ Tf~'. f 3 N 0422630
x C.- ,.^:t
E.3rr,pits oi Ph]rr..]cJK7neS1; Jr.Z i,!e:r C .,. _.._ .
HJr;r,1
_.=D:bromu:mtr:io~+r~~ptu^.~mtJt ~DB.\PAt. RJ,^:,:
E;trninatton 3nd Eaten~i.e Dee:a;.v.un ::0
=.4Dtnurcphtmol IUNP1. Lmtv
F..u;tdJu the Dti(erence in Sl+ectes S,is:ept:bwt. :: :`.:
CJuracto¢tn,c A;ttvrtv ::3
De;jbromudiphen.l Oude tUBDPOt:,+.J 0;:3t- ...
I tOBBPI Ltnar Phjrnu; Lsc_ S: .. ~
Curt;puund tor ReseJr;h 3nd Dc~ciuDT...' ::t
:.3'.3 Tetr~thl,~rndtheniu/+,au~tr, tTCDDt L.-.r_
Ph3rmJ6:oktnetra Used to Asetss Paten:.3; ror
lJtwn inJ ~\ssu.utcd T",.i. Itaiard
Pent3;hiorol+htnui IPCP1. Potenti:il k+. r I:;.
B>d. Bur,fen Js C3I;ulJted b%
C!u:j:tert/c PtiJrmJ;uktn.tics :3}
t:..: T
\, cimear P!:Jrnuc%'k:^.u;s J::Q S: ,:es'J ....-..es
_:3
~ `r.. Ch:oriJe tt C 1. \,1niir.m F: ..,;s. T:... . _ . _
St-jd. in¢ Phm ma;uktnttics .» I ^. :i 1
U:hcr Cft^i:;Ja. Ehde,,e wr ab
:46
- = Tetr3.hl,,rubirhe^,. S ..~c:.... s .:'. . C ..- .
~ s :n F.sh :4'
S :s:..j, ks:e::s :50
:50
[v^e~mcncJl Errors :53
Pjrj^e:er :53
P ..a:.. . Pa:3rneter Est,:^a::s .,5
.¢ \3nrneir :00
C .-,J~tr¢ Nv3-:erc:s
BjuJ;nc inJ '% :o.
E.;~trt^tcn!:: Dcvgn :65
R:icrencts :06
PART IV MET>BOLISH AND BIOCHEHICAL TO\ICITti :"1
CHAPTkK`+ R3droautoenphic Methods (or Phsrologtc Di%pu.rttur, Jcd
Tuvcolog. Studies.
h`bcrt H. Liss irrJ Chorles J Kirisler :' 3
Cp/ R 1 1l ! .r I' 26-23M.
a
Corrrnrt ti
Introdu.t:an ?'3
Me:hods :';
.ap;l;a:tz,r,s ="5
RJdio3utoe:].f:t; Sru~ies uf Drue
:'Y
N? ..c J.~n S:J~1,ri o t D.: U~Ir:C :j n :50
C::. .Jr R].':v]ut"trJ:fi~ :s
:
:S:
Dr.IT H]!~
ti :r. T:~S:.di =J1
E:c.. ur :91
E.~: .,. .. . l'. T ....t::es :93
~I Fe.. S:._ cs _a6
P r ..._ ~ : .
R:~. T .,
i D .. . . :00
~' ._.. ;01
R: . . ... 304
/I
CN aPTER ! 1 Siemfi;an,e of \tetabolrte\tedtatrd Tovcrties in the Safetv
E~]luJtaon uf Dru_ee and Chcmi;ih
r.,...c 30'
_.., n 30'
µltt.h F:re:.n C. mcow,Cs 4re
309
P]:hwa% s lea,!tne to Tovc \1etaNelites 309
4c:r.3uon Dr Epuvde FurmJ:wn 309
A,uvvton b~ OvJitwn vt a^ .: .s 315
A.tnnon b\, O:htr P]:hMJ.s 31,
A,ttvvwn tl the Gastru:rtc,c.r.3i TJ,t 31"
S,te of Tov::tv 31ti
\t.:Jbuitte Tovitty 319
DJse 3:0
P']sir.3 ]nJ Ttssue Cjn;entr3tions 3_1
Co~J:cnt Btnd:ne 322
\t ~. ..rs ut Due 326
Orhcr Drue InterJ.t1-1ti 3:g
Ut!:er FJ,tars T!:jt DJe
\1t:]h , ism 3.9
Is:-.ited Celis.
or S.:ten:, 331
(.r f R f f f"i 0`"f' .i'`.. 633 2
trr il#::ta::
T: , nc :hc SIeta ,:.:e )r 7.~v. ' 33=
Dri;1 Destcn 33_ -
:t i Tov,tt. ~`ter ~n U~cr..~e 3.i3
S::r:::r.u:y 334
ketere-t;:s 335
CHAPTER I I Intestin3l Drug Metabolism and the Broa%atlabt!ir% of [lrugs.
C. !. Pantuck. R. Aunt:mmn. aprJ A H. C.;nne, 34;
Introducuon 345
F:ie,t ui Crprette Scrowe »d Benioj,l; ~aae ,.. ..
l:,::stin:l Met3baltsrn of Phena;ettn 3;ti
E:;e;t of CharcoalBroiIcJ Beef on :he I;;:es:e-a: ut Phenaceun 354
'
Etr.;t of Rat Chow. Ve¢c:.b!es. and .:r. ~..~ 0:..
l.rdaIts on the Intestinal k1etaboitsm rr Dr is 3:5 ~
Efiect ui Drucs on the Intestini! s-
,rnJ Hcvrbirbual 3S'
C n,inswns 359
Rai:ren;es 364
CIiAPTER ;: Di,tnbutiun. Metaboltsm. and Pennatal Tou:u- of Pes:.;:Ces
..uh Rc(erence to Food Sa(et. E.a!wtjon 4 Re%teM of
Selected Literature. /1. S A'%:era 369
I:;I r-oJu;..:n 369
R.,c .i %1e:j^voc St~iC.a in Ta3' :c~... , ~. .. .. 3"0
0z.^".h;onne Insc;lI;rdts 3"i
DUT ird Re'.rteJ C.,:r.pour.ds 3';
a:-'-:n :r.'. D:e .'.rt" 3..
H;; :~...... ,tcJ lie^:a;',lor E~_.... ."
C!: If,~j.,,e 1~Q
L.!,.:jne 3S1
~t: .. ~\ % ;h:c: 3S:
C : :;r 353
T.~ ..~hen e 3S4
D!. .~:: i 3S4
ErE dosu 1 ~3 n 35S
Mtrex 3;6
F1i.:cnx,ed Bentc^ts 3145
Hc~7;h;orooe^tere 3SS
Ptn ~r.....r,%benttne 3s9
C.iroamites 391
C.rrb3r.-I 391
Doluo.vom.ttes 393
Tlrrrarr. 395
c~'R f fN 0",'~~ .~~'1
Con renrt ciii
Ferbam 396
Phenox%:ictd Herhtctdes 396
R::'eren;es 399
PART V TRA.NSPLACEVT.A:L TOXICITY 421
CHAPTER 3 Transplacental Toxicity of Diethyastilbestroa a Spectal
Problem in Safet~ E%aluatwn
J- h-. .a thL.urJn .P:,1 R h,-r L. D:x,:t 4:3
423
^ e:~.'st::~escro; l sate 4_4
Pti:r-ac.)JoT, ut Dtt:ti~t~;r.tiet'r:i 3.
R::at:C'i~1JD 1 )I' ...ft :J ~..:~:~ 3~
C i .In.1 %1e:ati"1 i:G
T. E ie;-s DES - H~r.:-s 4 3
T~._ ... f. ...+s Dt S a-.. _ s 435
-W I
R: . .:s 442
.4J
CTR ~~~~ 0426-o34
Chemieal CGrcinotenait in Srrtan Hamuers 147
C
EraomoTO et ol. (36J in randombred hamsters that had consumed about
300 ma of MC in their diet during a period of 10 months.
Age of the experimental animals at the time of carcinogen administra-
tion may also play a role, since ToTH (1ES) reported that higher numbers of
forestomach papillomas developed in animals given urethan at adulthood
than at birth. On the other hand, more intestinal tumors were found in those
hamsters under treatment as newborns.
In studies on anaer of the colon, the use of hamsters has also beee
minittul. WasaUttot=tt's rsview (194j only mentions that !,2-0imethylhydra-
sint auses colon tumors in hamsters as well as in rats and mice. To7tt (lf3j
reported that the incidence of these tumors was especially high in the txcura
(see'Liver'). Cyasin, according tn Htnot+^ et el. (7:J, pt;s;d fewtcr iniestitta)
(and rettal) tumors in hamsters thalt in rats (see 'Liver'). In our own MC
feeding studies, more than half of the male 15.16 and 17.20 BlO haauurs
had cancers of the large intestine, while all other strains tested wen relatively
resistant. So and WrNDttt (176J observed two invasive adenoarcinomas of
the colon in hamsters dying on the 2S7th day of an investigation employing
a.eL injections of 3,2'-dimethyl-4-aminobiphenyl (sa'Urinary Bladder').
Vitamin A palmitate prevented the induction of arcinotzta of the pmo-
intestinal tract by oral DMBA (19J (as well as uterine, cervical and tracht:o-
bronchial carcinogenesis), but So and WrxDttt (176J believe that this may
not be so for the lower intestinal traet.
We (Hoitovtteett et al., 801 failed to produce any gastrointestinal neo-
plasms by the feeding of 20% snuR in the diet, even though the aaimals of
the inbred hamster strain used wers susceptible to 6utrointestinal cancer
induction by MC pvaje.
CHU and Mwta.caw (1l): 71n oral ada+inistruioe of 7,l2dimetAylbeaamlvaeena
(DMCA) or t,auo(a)trm+K (l+10) to Syrias Itanstsn Induad dys6aatotic Itsioos and
earcinoma of the ronuon+adt arb srnaL intatina but only tM DM IIIA irdund drskaatotie
ttsions o/ the aoptu{ts Ysu+tinS tM o+ains aervia of SYrias trn+atets witti DM OA induoed
perinnl stia and.aSinal qreinwna in 100% of tNe a+aieub and eavid nreinoar iu 22%.
In animab similarly tntsted voith DMBA aP the addiuoo ot 0.!% vitamin A
polmiuu to the diet prevented tly denlopnatt of wn5noero ef t!K Sawoinaatiual tract;
adding the vitanun A polmitaM to the tlwd tsteJ for paintinj the oa.u Ore.eoel the
dOvtlopmtM o( qRiOolrle of Otqria and vapM tfM did not Inhibit ft deretopnent or
orcinan. of the tx++++nl stia The imptiession of the inlsit+itory a(i.a of vitamia A on
the induction ol apuamous oa(t oreirotn of t4. aweov nten+txsne i. tJ>r tsueatar i
eonsidersd. (Authorn' abutact.)
DruA 1Mr. (261: Administration by stoenaeA tube o( )6.30 dosa of 1 tTM of
20mrthylchotanthrene to S)rian poUen baeenten tardwd in tAe oavm,tes or.awmow
a!1 tumors of the foraiornxh, adenaareinanas of the unall and Lar=e inteiune, adeno- .
I
~`°~mR ~~~~ +~426~'~
E_1
Horrnacte
148
areinornas of the mammory glands. U+eeorws of the ervaries, and sebaaous wmorsa(
the skin and eer dutrt glands. Of these types of tumors. only a fetr spwmous cell pepil.
lomas of the foratomach were observed in control animeFe. Inflammatory ksions of the
intestine with hyp,erplastic and atypinl glands were a common WtdinS in both ewpcri
mental and control groups.
Durm.u and Surr;.. (33J: To a.Spr: . the lumn. of the hanWer efophagus, poly.
ethyk:ne cvffs wsrc surgically implante0 around the..opAeps juu above iu junetion with
the fortstomadt. This procedure resulted is atrophy of epirhdiuat at the level of the cuR
and pro.imal dilatation af the esophagus with hypertrophy eti muscle. lnuo(a)pyrene
(lfP/ in dimethsl sulfo>tidc (DMSO) eshlclewas instilled twia.eekly for 5 weeks in the
esophagus of hanwen w;th and without the constricting suRsft and eventually Rwpiaoma-
tnus lesions and stypias tkvcbped is the esophaius and pepiUomas in the lorcstonuch
of sonic ef the hamsurs that survived to ys orer 1 months. Though ksions developeJ
in the esophagus and foreston+xft in hamaers is both groups treated with DP, there wrre
differsnees in the typn of ksion. and in s+nirel tinta. ln the esophagus. a papillary tar
einoms. panillomatowm and an ares of alluqr etytw de.dopW in 3 of 1 hamsters with
constricted esophagus; a papillema and /i.e inuanees of cell atypia deveioped in 6 of
I t hamsters with nonconstricud esophaSus. The aSa of lunnten with ewphatcal laions
in the constricud group a.enpd 6.3 months kss than in the nonconstricted group. In the
forsstomack, thcr...n fe.er O.pillomu ar affected hamster in the constrined group.
even though thex hamuera.we 4 nsoetha taldec than thoosewitM qstrie pspllontae in ths
noncomtricted group. Cssrrie pepillotnef that h+d oroSrassd to eantinana stsre found
only in hamsters .+tlsout eonstrinioa of the aepAtSue.
Ewt*roro n d. (36J: The eemperstM tardnogenieitiat of 2aeetamidoAuorene. 3.
nr+ethykholanthrsrte, and 2aocumidoQuorane plue 3rnethylebolantNrene iri the hamstv
.+ere investipted. Unlike the eaaewith ran, eo iehlbieae of tumor Induction was observed
when 3~hykboianNreru was fed to hamsters sinr<dt;neoutlywith 2-ecsumidoAuorsrx.
Combined fecdinS or 2aeeuntidoAuorene and }or++dYykhoiarJthre>+e rasulted in adeno
orcinoma of the intrahepstie bile duev, penaatie aderoourinon+a. and mesentertal
sarcomas. while benipt cysudenoens of the intrshepstie bile ducts were the only tumors
observed in the hamsters fed 2,awumidaAuerene alone. AnaFyus for urinary meubolita
of 2.aceumidofluorene rewkal relati.e(y IutN elfa! of 3rnetAykl+olanthrene when fed
simultanoously with 2oeetamidoAuorarw. Likewiw, the continuous admtnistration of
smnhylt hobnthrsne in the diet sinwltaneously .me 3-ecsumidoAuortne aused no in
aease in the hepatic N-hydroeytatien at:tivity in .iiro aa compared to that of hamsters
fed only one of these compounds. One oossibk expt.rouon of the synergistic action of
the combined foedinS of Zaeaamidofluorens and 3methykhotantbrene in producing
tumors in auahepate tisirres is that d'+aary, 3nsthykholantltrats enAanoes the N-
hydroayladoe of 2sanaeudotluorene is thess tissuei
Hta%oLo (661: 23 rrq of Nh1U is 0.1 ml of nterwere given intravenously monibly
for 3-4 tt+oatM or I m{ NMU in 0.2 tal pnr..rs Siven inuat+eritoneally at weekly imer
.ek for 4-S months or tnuapsuitally, twiee a wark, for 4 months so groups or to Syrian
Aamsters of either sa. There wae 43 eonuols reooirinS no treatment. 'The sdenoeareno-
eus of the intestine isduwd in Syrian hamsun by N-mnhlINniuosourn (NMUI wcre
of two hiuolo{inl types, supe+flcial and intatinaL These types had distinctive characur
luits reprdinS pattsrn, q-toloSid fawres, secretioe of muao, aed trode of powth.
L..r ~f f`c. Hf''f S...l `W' 2C°'..It 3G
tk
/t,
Chemical Carcinosene.u in Syrian Hamuers Ny
The histolo{ieal eAanses induaed by NMU In th. muara of the smaG intestine diRar.d
from .rAat has been desaibed in sns"ie intestinal adenoareinoma and prolUtxatist
Dcitis of Syrian hanuters. NMU produad al+sration in the vitlous areAiunurn and cyto.
logictl change in the absorptive alls. Thers w as marked shortening ot the villi and
redueed thickneu of the muco,a. Tho vill0us absorptive od4 wne larip and e.boWa)
witA «ntrally placed nuclei.' (Author's sueurury.)
Hta.ct (71 J: While N,N'.limaMylniuosoucea aused tsawoqe+tic arlto~ h rua aud
tslali6nant thymomas in mia, this supttanot,when given to 34 Syriam haaewvf of both
twa .eighin6 90 S!sy m injeeGon In doaea a(r0 to{/kt body .*.pt, a+..d (is 17-)1
.eeks, avera6.21 weeks) 23 pusnatr odl earonauew of the forw+en,asA (b6'.:). nans~
as,.ry tumors in 79% of the fsnula and 16% of utarint oervis tMnortl h.or.at.e tuators
(adenowrsinomas, 11y.), cAolanpioaranorna of tAa 6ver (24%) and wbatuwus t+ar
comas accvrred in 6%. There were also OeniS,e averaoutt Aerrwpomat of t!W spn.n,
hyperksmoais of the foeatom.cA and sane tssa of liva sirrAai..
Hww (72J: Carcinogenic eReta of N.N'dimahybwtrosouma (DMNIA om mia aad
laurnsten was studied. Rcpated subrutanaous injeaions of DMNU ravlud in the iadua
tion of taali6nant IympAomua with an incident.e of 100% in adult C)H!M11/Ki mia ano
ieWuad malignant tumors of fonstanoM, mammary gland and utsns .,Ih a high ieei.
dcnet in adult hamuera. Control uumals aho..d eo pet)wlo6ieal ehanps. Eleettoa
asieroseopY revqled the pnseena of mtxies type C ras panido ;a sane of the tissues
eaaminad. Many type C virw partidea .+re found in a transplant of DMNU-i.duod
mdignant lye+phonu. Some type C vins p.nicla .ae sLowe in matGpnant lympAornn
and lymph nodes of ineligrum lyrnphornrbeving mice. A very small nwnbn of type C
virus partides were ob.crveJ in thymw of oomrol mice aed bone rsarre+ of a moli6nast
IympEomabarfnS movst. A few pattic)a, quite similar to murier tyyt C viwa putides.
Wae deteetad in DMNU-ieduocd nummory adeeonrtinoeut of hamu.r. No vinsalika
panfc4s were saen in mammary glands of control Rsntattn}, WhetJwr tLtaa pvtieb aro
merely pusentcn or are playing a sipdkset rola in the earonod.n.ir M these wmors
rsnuieu to bs detertnined.
Htaow.r.L Gf3I: TMes Reupt ornew~borw luoytas ntsi..d a sirtdl* as:+Jeaioa
of 0.2, 0.4 and 0.6 mg cycssin/6 body weight within 24 M aMr bint T.o droua ot
adWt
hanrters aeh received one doae of 0.1 or 0.1f m=cyosieVi body we+6At by stomach tubc
Awther three groups of adult hanwers e.raived two to rwr dowm of 2.1 .y ernr.ie)6
body weigAt by stomach tube at ietarvab of I montA.
TAers was no sipti3nnt difRertnat (s tlft Isadence of tumon bennw m rlorn ud
adult hamsttvs rocsiviey a ainih adnvnistrstion of trasie and ba+ar aduh s.rrtsten
reot:ivin6 s+n61t and rapeuod administntions. Hortvar. adult haesmt r.aeivin6 the
larM unpk doae o(c)casis showed a lipher ineidmas of tumoes tltaA taoaa t.oeiv~ the
amaUer single doss.
The most importanM ctanles induoed in lanwees with tyonw ..a taes a the li.er
and eonsisted of proGferati.e dunpa of t)tr iraalseptit bih duaa. M. dra euainomaf
v.crs aoducsd both in newborn and adult hamsters. Although Aepaoaeltntar oueinom.a
vs as readJy induoed as bik duet arrfa+oenu in newbora Aaauters. lspatoadlukr ear-
eieonus weae not found amonS adult atsimals.
Eight li.tr tumors induoed by qeasia wt truxplanud, and 6ve asmplteubk
tumor lines w're successfully esublitAed: Four lines originated in intratKpatt bile duta
CTR Mt~ 0~'~~~"~~
Hanunctu
IS0
arcinomas, and the /lftli originated in an anaplauit: nrcinomt. Owwnably of liwar11
oriSin. Kidney and intestinal tumon, aitidt .ere frqueatly induced in rau by cyw;n,
wete observed in a much lorsr incidenae in hamstses.
Ho«nnteca w d. (71iJ: Invasive adataordnoea of the tlandulu aomach wu
induad in 3 DIO 17.20 inbred Syrian huroten by the adntiniuration of I ppm N-nitrosa
dicthylamint' or N-niuotodinxthylemint ht the daintieS wta, and in 2 210 17.16 and
! 810 72.29 inbred Syrian hanWaa by p.ap ef 3-prtbylehelanthrsne In oontrau, many
other similarly trqted inbred Syrian hanater lars did ta( desslop areinoma of the
gIandulir stontaCh. The glandular MonHChf; Or rats and n1iOt are rQfiftant to potyc)tlit
hydroerpen areinofsnaa; hotreve., the glandular stomachs of taertain inbred Syrian
hanuten develop adanotareinonta after polycyt:lie Aydronrbos Pvar. This work dan.
t>futrated the intportance of genetic factors.
Ho.ovaen n d. ( I p): Seo p.K IOS.
So and Wn.roct (176): 2.2'Diatrihylj-astinoliphenyl (2,2'-DMSA) was adminis.
te:rod subcutaneously in dow of 100 tnS/kS body sisht to Syrian golden hanutsrs. Of
20 han.uers that lired over 158 days, 1! (12 fas+ales, 3 tnab) devdopedbkaJJer tumors.
In addition, 2 adsnoareinomv of the eoloe. I malignant lymphoma, 2 numnyry car.
einomas, 4 pranulosa.tMa eell tumon of the ovvia, and I spwmous cell arcnnoma of
the skin wsn found. The nKSn tasmulativo dotr and dtyf reouind for the indueiion of
bladder tumors were 2.400-2.700 at!/kS bQy.eyfn (I6o-a03 ntShnimaU and 260-)10
aya. We belias th's to be tha ant t.pat of Nn it,dtxtien ef bladder tomon in Syrian
Soldts hamsters by 7,2'-DMlA.
Smv.ar ( I t I ):T1n tok ef a Sentt, tilona or bt tanbination, ddeh produce adeno
nreimmma of the stornach in ssperierntal aninult is ravie.od. Thtst ineludc 3-methyl.
Motanthrons; N,N'-2,7 ; N2-Auorenytacsumidt: irradation;
alfatoaieu; elaiomyein; N-mahy4N'-nitraTr-trva~oSwnidier; 7,124imstbylbuuamhra-
oene, and N.methyl-N.nhtoaeN'roetyhla Ineidaeotr, aitria for diapasis, and diRtrent
routa of administntion in n+ioe, ratt4 SuiMa pip, and bnwen an diseusud. 7Ae ob-
ter.ations in apsrimental aeinuls am n1.Md to tl» Otebla+e ot hueua nnoir. (Author's
abst»a.)
Tont (ItSJ: Ten suEeutaneas iqjaRiona of I try trethan/i body reipht wers
adminstarsd .skly to Syrian pldal hnmunt at bitth and aduh aIe. Significantly higher
numbers of foratonoch papliotrri de.doped M aa4nt,h tNt btpn to reol+re urethan
at adulthood than at hirtle, tevsn though tltere .ern similar incidences in animals having
this lesion in both ap,e groups. On the other hand. appreciably more intestinal tumon
were found in those hanrtera ttartinS to reaeine the tnatnrm as eswborm than as adulu.
In addition, dermal melanoeytonw and thyroid, Ia+S, and some other tiaue tumors s»
iebuoed without any apparent diReeena ht Lmidmar in the mo ap Smps. In contrast
to the effect of a single nreieapenie dow to .hieA oNy two tss+w nspor, 4 d- wwa1
additional tiutia develot+ed tumors wha elalksnpd by r.pntod injeaioro of wstnan.
Eithn their ttaTon6enio thrahold doie rY higher and they tkaded pniodic stimul~ or
morphotofie and functional dsvebpnrnt ou swt at an appropriate stapp for tunar induc-
tion at the time of the single injection. The possible sR.a thal tIM ap of the host has oo
tumaipenms s discvsud in light of the teulu obtained. (Author's aEuract.)
Waasauaeta (I91J: Colon cancer m are almort lkrtaroly If induced ey a+nra+-
etenW facton, probably consumed with (ood. Exspt (or ana lrpd of hunsun, ooioe
CT 1'`. f t N 0 42 6 3 8
is
Ak
CAemial Carcino=cnesis in Syrian tianwen 11t
anar b inheQuent in taboratory or domatie animals. Reliable induction of eolon anev
an be aehieved with two broad dasses otehemlah: (t) derivativa or )rneshyt.4amino
biphenyl. and (2) dcrivatives o(1.2dimethythydrazine. including the plant product e)essbs.
Somnimes an unknown ingredient of bracken fern auses aeat or colonic anoers. Yhe
nrtabolism of 4-aminobipheny I derivatives invotves, among other eseps, N-hydroq'tation,
eonjupiion of the mctabolite with plucuronie acid. waetion of the conjupte in bile,
liberation of the free Nhydroty compound, the postulated astive imermediau, by apian
of tsacteriat (lora in large inteuine where reaction witA sipti(kant tiuue, esU. and srotav.
!v eMments aocun. After oral intake of tyasie the aSlyeorr u+ethylasosymMaaol ie
likewise freed for raction in colon by bwterial enaymea. 1,2Dinxthylhydratiee yields
alosymethane which is hydrozylatad in Gved s:onjupt.d with Slut:woeie atid and aeeresad
in bile. apin to be split in gut with liberation of the aaivc meUtytatwtymethanol. On Ae
buis ot these models. colon anar forntetion ir man nuy involve: (1) inaestion ef rvn
pla c~reinoaens with dict, with liberation of the ative agent by bacterial .ntymw;
(2)intastion of proareinoacns. absorption, sntabolism by li.er, ueretion in bik, and
trsing of active a{mt in Sut; ()) production ot active agent by f>eteriwl fkn In prt by
eonvsrsion of seket food precvrson, and (4) production of a myeaoaia by an ieuuiaal
tt+icroorpnism. (Authot'a abssrut)
X. Liver ond ailiorr rrecr
Carcinogens which induced adenocarcinomas of the bile duct included
2acetaminoAuorcne (also in combination with MC in the diet) (36), N,N'
dimethylnitrosourea (71 J, cycasin (73j which, in newborn hamsters also
caused hepatocellular arcinomas, and 1,2-dimethylhydrasine (l,2DMH)
(Id6), which caused bepatotttas artd liver oell prtaeottus,. Sometimes it is
diRtcult to distintuish the two latter lesions from each other, and one ease
of a benign 2acetylaminoQuorene-induced hepatoma was teported that,
upon transplantation, was found to be highly malignant (17j.
Protein binding of azo dyes has besn compared in IC and C3H mice,
and hamsters fed p-dimethylaminoatobestzetne (22). The binding of the dye
was found to be somewhat related to the tozieiry of the dye for the tested
animals, high in C)H mice (susccptibk) and low in IC mice (resistant), the
resistant hamsters being intetmediate.
Nitrosamines, speci6ally DPN and ahydrotrylated dipropyl nitro
aamine, as well as MPN (S) induced hep.tomas when given subastaneously,
but only MPN caused also esophalleal squamous nrdnomas.
WlrscHu (t97j studied the biochemical eRet:u of s.e. dosing of hamsters
with diethylnitrosamine and found that protein synthesis and aryl hydro-
carbon hydroxylases were affected differently in liver and lung.
It is of interest that hamsters appeared to be more raistant to the
L..M i R i' --AItr 3 0 42 6 3 9
b
Howauaca
A 1
®
hepatocarcinogenic effect of aflatoxin than rats (67J and that the only tumors
produced in hamsters by aAatoxin were adenomas and papillary cystade-
nomas of the Harderian 61and. It is unfortunate that tbtse ttudia were done
on unspcci6ed hamsters and that it is therefore impossible to know whether
the described resistance is species-spet:i6c or genetically detetmined.
Other substances found carcinogenic for hamster livers were atethyl-
hydrszine (1881, and 1,2-dimethylhydrazine Siven.in the drinking water (1 i7J;
they produced, respectively, malignant hiuiorytomas or hepatic an=io-
sarconus in the liver (as well as in the lun6, muscle, heart and pancreas);
2-hydroayethyl hydrazine in the drinking water caused bepatomas in ham-
sters and had no carcinogenic effect in mice (169). NAwsAtct fr at. (124J
noted that hamsters were resistant to dietary be;nttne hesae6loride, which
caused liver tumors in mice. Rats also failed to respond.
Gallbladder carcinoma was induced in hamsters by truans of dimethyl
nitrosamine combined with cholesterol pellets implanted into the gallbladder
(13 out of 19 animals), and in I out of 16 anitnals receiving only DMNA.
Diethylnitrosamine with or without cholesterol pellets caused no tumors 1951
AirMOn er d. (S1: The metabotie activation of ahroa aafffettnda by a(tydro:ylan tion ie .R(1
keotre. To explain tM t+natpatad eabytatioo obwvad aMr the adminis.
tration or rarioue nitrao compounda to rattti additipW tKtabel'stn by `.Aydroayl.tion
has been wssated. Experiments were therelore desi6ned to eompare the esrcinepaie
eReet on rata of di-n-Oropyinitroumine (DPN) and ib Deualat.d nrubolites, bbYdrosy-
propytpropylnitroaamine (HPPN).
(OPPN~ aod u+stlty{
peopylnitrosamine (MPN).
Each e:perimenu) aroup eoas'stsd ot 10 arM aed 10 foe+d.12-wk-otd Spra6ue-
Dawky ratu. The aninub .we iAjacted subatannow/y ona a sk for the duration ef
life witA doem equivalent to 0.2, 0.1 and 0.0! LD (LD..: DPN: 1.417, MPPN: 1.273,
OrrN: 4:4. MPN: 106 testkS b.r.). WiMin 6 e+oetAt of be=+ntini tbe aporinw+t,
aptxo,tinutaly 30% of the rats had died. All compounds had induoed tunan or the
liva arta S months of treatnxnt. TM neoptaun..rs tepetpra and tttprataotuular ar-
einomu;. After 6 months or treatnKttt, tumoes ef tAe e+oplrsut.ots ane onh Lt animats
raceivin6 AtrN. HicatoeiaUy. ttwe .era squamous oW peOfttoeaf and tuntini:ir+a
squamous ail carrinomai.
Thw preliminary rewlu indinu that }hydro.ytation tu+d qdfsepuatt aepe do not
alter the urcinota+icity of DPN. Similar mudiawith Syrun golden lunrten pve aimilar
retiutu. The neoplauro induoed in rats by aHPPN and b-OPPN desloped in Me eanr
orpne as after DPN applfntion. Ha.ever, aopAa6sal tumors in ratA altheuah twn in
otAes aperimenp, h.ve eot yst besa found artsr tr*sunatwitt1 tAe "Pdronr4ted eom-
pow+ds in out aperinrnts;.
Dectiarr.a and Mevwrta (221: We studied aso dye binding to proteins, and at the
wme time atoraluctase and NADPHsytocetrortr c roJunase activyks in Me lirver of IC
and C3H mice and hamstern fed DA1(~dimetA~batinoarobenaene) orer a long pterad.
Sauhivity of C3Ff mics to the toztic effecn or DA! and raiuano of IC ntia and ham-
V T R VAIN 042640
Chemical Carcinopenais in Syrian Hanwen 133
sten wers tronArmed by histolupiol wminasions. After 3-3 wals of DA{ fenlinp, tM
amount of proteinbound aao dye inernsed pradually up to 6.esks, then remained rwrly
constant. In control animals uoredut:tase activity was Mv times higher in IC miee than
in C3H mia; activity of hamsters was intsrmediate. NADP1iaytochrtrnr c reductasa
aetivity was nearly the same in all three poup6 and was in eo way related to atoreductasa
activity. The sensitivity of C7H mice to the to,ae efteeu of DAS eoaJd be eaplained by
tAdr weak a:oaducuse anivity and Si61s level of aro dye bindinp to proteins. Ott t6a
conuary, high nzoredueuse activity iu IC mia would allow anosicauon of DAD aad
prmnt or delay its toeie ef1'eets. Resistana o! hamsters oould be linked to the amll
aaaunt of proteinbound aio dyec yet It annot be explained by thsit weak umredut:tau
aetivity and probably depends on other mwbolie proasse, .hrch have besn oonaidend.
8r.oroTO er tl. /76J: Sae pap 141).
Gtasu er N. (4t): we reyon a highly tnuignant transpbntabie tumor. derFved from
the )iw of a h:mster fcd 2-aaty4nunofluorate that did not appnr nsaliptans : the
donor. A piaae of liver tiuue was «anap(anted into three ntck wnlutE hamsten; 2 mentAtt
bter, all three developed mana at the site of trarrspiantation. The neoolasee was a Mnr
multinodular white atinss, Ibstolopially characteristic o( scirrhous comnoeu. Hannsers
with transplanu of tumor tissue, oaU susqention, or all euqure all developed a AiShty
maliznant tumor. Thosc with tranaPlann of soniated eelli, piaoes of liw from untreated
hanwxs, ard saline injections did sor develop neop(astie powhs. Tnnsplonts through
30 pattsapes .ers viable, hipltlY tatGptuu, and maintained the ofipinal wU type.
1iu.ous 167): Allatoain adminatend to Syrian haeutas, intrapastrioUy and intra.
peritonnlly, induced lesions of the liver, kidney, small intestine and periodontal membrur
of the incisor teah. Tumors of the Harderian fland Aad tw histolopeal p.utsrm, solid
and papillary cysudenomas. Eaithelial nau of Maluses.vc naed ut the psriodontal
manbrut<.
Focal hemorrhagic t+eaoais, bemoaiderin depoaits, sne=afoeytosis, aad bile dut:t pra
liferation oo:vrted in the liver. Tlr rmal Maion was eharactaiaed by eytomeialic drstp
in the proximal tubula. Histologically the small inteatine revealed alteration in the rillout
architecture with marked shoneninp of the viUi and reduced tbicknas of the mucosa. The
villous absorptive e:lb were cuboidal with oentrslly placed nucki.
lisa.rt [11/: See pap IH.
Hieow a d. 173): S.e pape 14f.
Kowsytwstu and Tooo (4!): Hattwas aith a without wrpcally implanted intra.
dro)aeystic eholesterol psikts wve Siven eardnoaen diethylnnroumine (DEN) or dimah.
yinitrosamine (DM Nl, dissolved in dri.kinE water. Eapowaes lo ehese earcinopero lasted
from 1 to 12 weeks. No pNbtadder twnon were found in DEN-tsoted banutees, with
and without intraedtoleeystie 'eaaerintensal uona'.1e LI'X% of hanwers eaposed to DMN
and having pllbladda pelkts, adcnoort5nonua were found. Only ane pubJadder tturwr
was detected in DMN.trated aninub who W t+e pllb{adder pdkt. It w concluded
t)ut 'eaperimental pllbladder stone' eNtancsd the malignnt tnnalormatwn of pUbLdder
mucou in DMN.tnated hamsten, tt tw considered proboble that d»olaw of bile duct
and pllbladder t9tthclium observed only in DMNtrnted animaJs retxesents a premaliS
nant lesion. Presence of this prerrtalipunt lesion atsocuted with nonsl+.c,lk irtitation of
ptlblaJda mucosa by a'uone' nuy be considered an imporunt euolop,cal faaor con.
tribuunt to rallbladder rtulitruncy in hamuers. (Authors' abwset.)
Ci R Hi 7 0'°'T 2a3 '°T i.
,
i
.ti
. J
Howsuacca
154
N.c.SAct er .f. (126): The tunoripenic eRecti of a dix containing the s-isomcr of
bensrne heachloride tuHHC) on the liver of vuisw aniaAab was es mincd. )t waa found
that s-DHC indueed Iiver tumors in mak and (smak atioe but eot is nu or hansten in
the present observations. HistoloSieal ehaases in the liver of mioe induced by aAHC M ert
also much pestor than thou induced in rau or hamsun, Male aaitieuflt.Kre more wKep.
libk to the tumai6snic action of a!HC then feeulet. As+onS diQaeat etrairo of mia,
the DDY showed pnwt wscsptibiliq and the CS71L/f nhe.ed the least. Induction of
mouse liver tumorf by a1HC ras not inhibited by ooncomiuWlt feedinS of /-naphthyl
isothiocyanate of,rby,arosyeropioOhenone. Howsver. 3lnethykholanthroee sliShtly ier
faibited their indurtioe by aiHC
SNt.usu and Tznt (1691: Solutions af 0.0111% 2-hydrosyethy0tydrudns wsre S1ven
condnuouly in the drinking water af 6. and f-Mekeld tnndombrsd Syrian Snlden
hamsters and Swet mse for the remainder of their Iifesima.le treated hamsters. 6% of
the fe+nelet and 10% of the males develoeed hepatortW, whereae among untrpted eon-
trolt the eortosponlin6 ine;dencs.ras 0% in tl,e fanakt and 1'K in the males. The chemical
did not increase the incidenes of otha tumors in hamsters nor did it result in a dcteeubk
tumori6enic eRat in mits Jrtyd. o.rahylhydratine iewiJely used te induce the lbwerins
of pineapple plants. tn .ie+ o/ the earlin reported tumoridasieity of thit compound in
miee, the sisni/ianes ef U. prwent findinp it ditetirsnd.
Torn (I1t6J: Solutieet of 0.012% hydraefne wlfau, 0.001% t.2dinuthylhydntine
dihydroehloride, and C.!!( i/aicainie aeid wt Siva ooetisuaufy in tM drinking water
of 9-. 7- and S-wekeid randomly brsd Syrian Vldea hamsters for d+e ra.rinda of their
lifetime. The eoruump+eo of hydrarne eulfate and 'soaioeunie acid .ata .ithowt any
sirnifkant arc+no6eaie .nien, .Atite 1,2dimethyfhydrstine dihrdrotitioride induced
an6'otueomas ol the Nsod ..ult .ith iaeildeaos of 19% is f.malee aed 112%ia auMd.
In addition, :t produced as apqe+riab:e aurnber of twnon ia Ur eeewa and liver.
Thw Mdin=s dnrfy show that the atciaoesinie eQest o(Aydraons tmlfats b:peoes-
dependent. Resulu abe n4iou that the .arioul orpnaro0ie actiar ot 1.2dimethyl-
hydratins dihydrothlor ide rhen administered by aaOtMf routs is Iha tims t;yecies could
possibly be due to diffarmt nwbolk psthwsyta.
. Torw (117): Studie .ae mufe on Ute aroepholoSial chtrscteriuita of blood .eitd
tumors induoad by the o.s. lifetime adminiaratisa sf 0.001'li 1,2-dinKthyUtydra>Jns
dihydrochloride in Syrian golden hamsters. TM laiotr w.re ehs;eifled as anSiaaroonw.
They em+rred ia 19% ot the fsmalee snd 82% of tb mua (with detns<in5 fnque+ky)
in Gver. lunp. mtueJe, heut, and ponaee.
crya, light. and d.etren etinptvpie and lituoclNtt+id) inNSligations were perd fornxd on the tumon
The .e»ero+eopie and light microscopic study t;ho.ed the typieal
appcarana of ansiararoenn ean0oud of rouad ot eloRpted polr~nal a.opiutlc endo-
Ihelial alls which fornrd weytsr oens aad delu. The hatod+emieal oork included the
deteftninili0n of eblkym IM1LhMr. ioniRnd irpa. 001 yYethtlRdh
slyoolie fatty aeid eauerK. end altaline yhaphataet en:ynu netivity by the ksion. The
fonnauoa of reticulum sad wn+sd iron was at"bk, while the amounts or the sairty
of the other thra t:ubasnaw .e.e fubuantiil. EUctron microecopic aamiaetion revakd
the ultrafvuewral daatit of the .uneut eomponenta of the vaeeular lesion iucludin6 prrt
of itf developmental ata0r. Heme+rluaie areas, structural eJuraeteristia of the an6io-
tr+conta maligrem endxwal odl nudns.ith duomstin arrsnSaroau, and its cytoa
COf R { f f 'f 04.2642
r
Ctrcmieal Caranopenais in Syrian Hanrtus 111111
platm with orpnelks, intratuminal atl eurfaoi, and contaet between neoplastio endo.
thelial calls art deseribed and illustrated.
ToTM and SNwizu (liq: A 0.01% solution otmethylhydrazine was aJminiaend
daily in the drinking water of bw.ekold randomly lrsd Syrian golden hamtaen for tAe
ssmainder of their lifetime. The treatment pve rise to malipunt hutioeysomas d IiW.r
and tumors of the cacum. Malipunt hiuiocytoma developed in 32% of the (e+natea aad
ia SN% of the mala whereas among the eontrob no such tesioer were t.an. The iasdeeee d
tumors of oaeum was 11% in fematn and 14% Is maka, eompand to 1% in the aantrols.
Macroscopic, light and electron mieroscopie, and histahsmital invatiptiom of tha
liver lesions thoWed the eharaeleristio appearana of erliptant hiuioeytenw. The hir
toloaia) involvement of the tiswa by the tumors is poaented. The nne w>,ettrt of the
eniiSrunt hbtiocytonu, the nuclei, and cytoplasms with orpndls of the tumor aW ars
deseribed and illustroud in deuil.
Methylhydrasine u a rocl:ss fuel component, and soer of iu drrivativa have baa
propaeed for use in usatinS anain human onars. Dr+ousa it has leen t+howt+ to produa
tumors in mia and now in hamsun, t+recsutiont should be taken cvetesrnini )u ttle.
Wrncut (1971: (I) Syrian Sotden hanuttrsWere treated with a single wlatatrotr
dou of 200 mS DENA/kS. In the Iiw Me treatment produced a eipninesnt and aary
inlulwtion o( the incocpontion of otntie acid ieto RNA and of tertane into prots+n. DENA
also lowend basal and 20.MGetimutated activities or hepatie aryl hydrocarbon lydrosy.
tase (AHH). (2) RNA synthesis, protein synthesis and AHH activity wsre atw e.aluand
in the lunp or the same animals. In this organ only protein synthesis was aRaned by
DENA. but not RNA tynthesis or AHH activity. (3) The Incorporation ef Mymidine isto
DNA was inhibited in both orpw earty after DENAtratmert and increased 2-) days tatar.
(4) Althoulh DENA. injected suheuuneouety, aetumulaW in liret and lung in to:ioobSf
eally acuve amounu, the acute OiocEonieat reipoires e+r the h.e orpne are not ideetloal.
xr. x/dnry
The induction of bilateral rsnal arcinotsta by diethylstilbesuol (DES)
given to male hamsten has bees eonRrmed by many investigators sod this
induced rtnal tumor is now being used in its transplantable form for chemo-
therapeutic studies (as s model for ehemotherapy of advanced huntsn renal
carcinoma), with S-Auorourscil appearing to be more effective than cyclo-
. phosphamide, dactinomycin, mitDramyda and viob)astine (23J. DES di
methyl ether also induced tumors, wherw DES toonollucuronide did not
. (98J. The model is also being used for ensymoloSial and immunological
investigations (11S), and in sophisticated investigations of its fine structure
1102, 111). Such studies were concerned with glucose 6phesphate dehydro-
tenase (29J which fluctuated during tumoritenesis upon elearophoredc
study and was found by Listochemical studies to be incrused in tumor
tissue, as was isocitrate dehydrotenase. Succinate and ~-hydroxybutyrate
CTR H N 0 4 2- G 4 3
I
Ha.nuRuu
ISf
dehydrogenase activities, on the other baad, were more intense in normal
tissue than in tumor (122).
KtRt:wAra 1901 found that none of his DES-iridutxd kidney tumors was
ever as hormoneindependent as a transplantabk, spontaneous kidney tumor.
Isoen:yme analysis may provide a means to distinguish between hormone-
dependent and -independent DES-induced renal turuon (2a).
Estrogen receptor studies have also bess carried out in thest tumors
(107). MtTUtit (116) claimed that eposidation of ths atilbene double bond
presenu a major pathway of DES metabolism.
Certain subt)e differences in estrogen binding by estrogen-dependent
and estrogenindependent tumors have been ducribsd by Ktso er ol. (d9),
and biochemical studies on hamsters bearing atrotsn-induccd kidney
tumors showed a deerase of hepatic 6lucuroayltransferase activity toward
DES in hamsters treated chronically with tlut hormone. -
Chetnoprophylaxis of renal tumors induced by DES lus been achieved
with 2bromo4trjocryptine metbaae sulfonsts (S4j, which appeared to
act via the pituitary. In tetrospxt. it is deplorable that the powerful earcino-
genic sffect of DES, demoutraud conclusively in 1949 (92) upon the male
hamster kidney, did aot prsvent the clinical uas of DES which led to so
much tragedy through its intrauterine eNects upon renal anlage tissues, which
in shared by the renal tubules tusd the va jinal wall (Wol!liso duas).
oa Kuwa+at.l. (1a1: DESiedwrd kiQaey tun+en..n traarpl.nt.d into the at
titsus of DESStr.st.d maM ltverwas. One ar'niaa eeW ana Ytjiaad and tueroes allowed
to grow for 30 days bdore tAft aaimeU rsotivad Lp. Injaetions of striM aline (control)
erery 7 days or 0.15 nqlkSl+vsk of .inbtaaiee. f aWke/dar of eyeloohosflhamide for
f days followed sy S mSlka/day ror S days of etitlrfmtsin,lS aylkgfdar o(Snuoroaracl
ror. ays, then 7.5 eulkS oe atternate days ror rour dosa t1+as dosage kltsdwlea .nrs
ehosat b.uws they aoreaspad to dinintlp r.oommatdad daats for bwnam. Cytosaa
and vincaistine nusad no tumor tnhieitioti fftwouraetl pq tM tt+at marked tumor
inhibition and caused aipti6antFr ieer.s.d tauvivaL MiUrunye.ia and daeunoe+yata
inhibit.d tuawr growth but did not aaat sdrvML
Dooca 1:!): Several in.estiptars InN ahown that changes eoew in isocn:yme aniri-
tia of laeuta dehydreaenaw (LOH) and ducpsFphoapAats dehydrota+u+a (GdPO)
as tiuues become neootauie Ae+ytsatids-iel atacaophoretie studies of two Syrian hamster
tumors havs demoesuautd eAaeM in ttte itoeeayrets Paturnt of LDH and G6PD dur-
inS tuner oroarasiaa A DES/tstewrarinduad aomt aland tumor devslopa Me
typical LDH peture of tealipunt tkus (Ai=h aonadttratioa o( tM ato.et n,ovine
Yaen:yme) as it oropares to itu Ana) arcuwtie aats.'!ha GiPD isoenry*+e pattern of
a DES-induced and DFSdepa+dent tsar) areisoea diRsn frorn tNt of an autonomous
Mormor,eJndapsndent .ariant dsri..d froen It. Siaoa aAW awop+H induad tumor of ths
kidney of ths Syrian hamuer w/kst dat+aibad. aerertl kramoaeindepcndent autono-
eroua variants and oes sooauneou reoat tt,mor ha.e aOpund ie K'uknun'a tunuter
L.r f f"',. f t f'f 0-"f' 26'."i. s..'.y.'
rl
Chapter 3
POTENTIAL CONTRIBUTION OF
INBRED SYRIAN HAMSTERS
TO FUTURE TOXICOLOGY
F Homburger
8ro Rrsa::^. I^.. :~:r
INTRODI'CT10%
I
T-e se ..'t,r, _. 3 s.e::es c' 5n;-na; `or .:t.,_,:¢: :est'^g -is
^tt., : A,,. :n a ~:.e.^..... _3i.s T J"~s
.'3^_C'S'1 :I ~':CJS ,.]sSts JI .:1,. ":3:...3 s in `'.;mJ'1 i_.'e::s Jt;J :J
s:3r:^ !Jr '~3t s7e;.ts Q! .lntr.,31 tf:3t h3rales !'he :t,1ss JI si^st3nCQs :0 ~C
... ...e sl-e ^3r^e: as man P e~wus:v. se:e;t.vn ii 'hie jr. rr.i!s 'i tie
-.a-- ~een 3rDt:rary 3nd not mu,h ,...ierent frim :he ^et!:cJ
Et-,;.::3n . -3r3o`Is ~Ar.o. xhen .:o ^:an. ~i .-.eu ..~ o :as:es
i+:.:"e.~ . . JCS :J .'J.J1t eS
f), j :r3 ; e:ed oi un;e rats h3ve been :he f3vonres oi tix,;olo¢tsts
'esprtc a h:v_h incidence ot disease and spontaneous neep~asms E.en now. r:ts
:o h3ve wide tox(cu!ogt~ use. espe:cj.ly s(nce pathogeniree
ar.,rn3is tiase become readily available. S1tce, too. have .een a irortte. espe
.:a;l% oi etper(mentil oncolog(sts.
In contrast to other rodents used in eiperu^ental pathology and toxt
co!eey srrt:e the dawn of biomedical research, the Syrian h3mster is a new
corner to t`:e laboratory The tirst s.tld Syrian hamsters (tiletocrrcrrus aurerus)
were captured in 1930 by Attaront (197:) &nd successfuUy propagated in the lab
oratory Through Adler's tnstit:,te in Jen,salem they iound their way tirst into
English and !ater into American research institutions (Yerttantan 197:) Today,
:r.ere lt;an I m;llton Sy nan himsters are so;J annually for research purposes in
The author's *ort tn;iuded in :hts rc~ieW Wos supported in par t. ISPHS jener.l
research suppon t»nt SOIRR-055:5 tDt~tuon of Resejrc!t Ij;tltr es 3nJ Resour.est .nJ
:scar,h su^,por: Erants CA I3:32. CA:SS33..nd Ca.I54:5 (Niricr Cin.cr Irsrt:.rt.r
end in porr, by BtoResear:n Consuttants. Inc . Gmbrrdtte. Masucnu.c, .
35
(..« -rR f f { "'f 042645
a
the 1:+::ed S,-:es j.one. Howe.e-. :n ::
rntce and IS m:i:lcn rats used euh .e3r In \-
han^.ster sail constlt;:tes a necie:ad :r.lronty' IT F n ,s:: :o
,reups oi :nlcl.e and tai'Jabie Jses of -Fe ioiden ~Jr^s:er. .: i
reierences tTao.e I ).
T>BLE I Ln,que and V.:wtve E1tper:rer.:at Ctet':r :!~e Hj-+s:e^'
1 Tirnot }ro.:h :n ne ntea cr'h ,on^t:~IS an: b...rt-zn . _
Srl.en. I't6I, Chure et al . 1952. J utten .nd L.tt. 195': Lerrlon e: a, L-:
19Sa
P
9
1
.t 31 . 1
$.).
htterson er al .
Tinscrzntarron cf -wunaral anJ st jJutt ^t.uet :n : ttt ^ouch H~r: r: , 1
Ye-,inran. 1954. waterman and Uohnus. 195:1. me:i rP:-r. 195'1 :..n -
:9!1. Re.n,rt :t A . 19bOt. pe-cru (Hou.e ct al 'aSt:. :. SAc
ia6:1..,rnr.onrc cc?ranrt 'Smrs:r and P3rt. 1951a5 t. I :Jr'::r :Dr:rr t,:
P-
C.fcrrmcnrA .atcrnn;t:ncars in ncck ;ou.n IGhaduilY and til-r,an. :y.; t!: s
I u61 . SzllcY. 1953. Snu6rk. 19f9s
+ T:inblanurnn ol n,rma1 +nd%or rnaht:'lrnl Irtwet n rtes o:'er :`An ;`:eee ;,....
sirn IAJamt. IcSR., 13. 1Jtmt el jI . 1956. I9ulrro+m et - 'ab -r -
S T.."+ ::antri,nu:ron 'Cab,%rn. 1960. MYets and fanajan. :iSS. :4:':: ~ R::c
I~S91
~ H ~1 `~r -lrtsrtNce al slu-I.et r^.Jonnr''a %usrol::r:e Dc a-t'e . . -
... .:r . A;,er +r.. T'aoCOr. 14)1 1. :rrv+sc'r;c >.le: :9a' f. .., . .. :. ..
. . :4+Sz. os. :c,a:oso!fcr+t 'Crarn tr.,t bcncc :n. I:+ S.-:..r . . . .
,l.ar.,, 'a+F, ReaJ. :95I. StunaarJ. l9+cr. :,cn:!r:a d:,s 3-..: -.,.....
+c+ H,hes srd Ak:rt. ~95:1
. $...tt rn .vlrpt> nd
~ti 1 on~, 19!+r. ,;+!,
U!^nr. et il. 19+0. t-.,1 , 19a1 c~ ::.t _.:r:;t R:a:t-. e
.-J C:nn. 1944.
4+1 i.lr. Sr Lo.rt rr:r:i ot,nt Br,,un el 3,. E?+:3 . r'.r-:: S:
, r ~ 0+0, P'.'tz et JI . 1 4I:. SlcoDrns 1'!J Lc-!an , =+91.
:A
-.,
. c :,N ,I . ,io er I . . i~:a '1 .,Orr-.0 ':.ia : n . .7+! i. - : r t :\1 M
.. .. ..
+ar ..rr `r:r t.:a. 1:+8. Rt::.^ .. : .~53;
S.~.'^ur.l~.^ct. '~r ..'+en %c;ntv 'a:,er
Jn t~t'~~e~fal Irrr,.. .'1
-ce Tz.a:nr e: i :ecl to,re Jt,/n. :i5: .. s. =i
S:.:c. a,d krev+oe:. I4S9,.
^ rrt 'w,te r+d !9eS1
~ Ke,.zrcn n ~c,e:,ct Rc .scn. i*5:: .., :ri .oT:t^^+rt C:... -
: .,cnrrrnt 'Orunl ind Psnskr Ia5:1 D%A :nC . . .r
:,'itn. loe,:r
M.Cra. 9!1. %1e,ers ;9'.v Me.r.s a-ij C't:::e: =!6
1451. S,dc!+3-1 ., al . 1956. :-. C'1. : 'Ic<i
I: he+n,:rn ,Bro.t 1 4003 + C~:%-eld :, L.-,t-. 'aS+ D
~:10 L.TIn and tz*.e!: 1~5+ \I:Lrre.1. 31
. ! .^tttmrnrzl ^N.1vlu~) r'O:N:nf ^rr':;Or .$^Ith arJ lZ:Ss al.:ZC,
.-O:t lr4-trnj RJ+IZnd .t^.j walers .Oler
1 3 INenlat ,..et ' a^r.J. 194: H.rst et I .349 Ae.es. .1`6 we,es 3-.
b Wrlchesl n0 Junnwn. l95'1
.
?
Repr,nreJ DY :hetmrss,on %reRS Ttit ll:ntrr e: Rue H' `-ac ?t..
Robinson, Ind IlYldt Ma6atnaes C IoWt Slate Lnr.erulY Press. Anus. I+t9
C/ R H/ / `.r' rr u'i..a id 7 is.P
Hamirer C1e in furure Tosrcoloj,v 37
TADLE I(cr .. -nued) L'nrque and valusble Eaperimental L'ses for the Hamstere
14. Cudtoeascusu resear;h ~nraocvctilarory studres (Fulton and Lat:. 1957. Fulton et
il., 1946a, b). :hromboembofu+n rCopley, 1948. Fulton et a)., 1953. Krvy, 1931:
Lutz et aI., 19511. are,oscleosrt (.altuhul, 1946. Coi.man ind Pollak, 1949;
Smith, 1951), .'r.e-ra tCul:en and Swank. 1953), esperifunr:f hpperrensron (Sttou
et a1.. 195+). c:d:o'+,voparhy I B»usz et aI., 19691
IS. l.'se in ;harms;aioSy lChen et il. 1945. GooJwin »d MarshaU. 1945. Harris et aI.
;9a. R,;;ers e: sl., 196?. York et L. :9631
16. Nuu:!wn:l st:,Cws .4 Jc:;:encv Hirs:..i. l950. SaIley end Bryson, 1957).
6uamrn f:^.J ^+usc/e Jecenrr::on -H:uch:n. t9t:, Nsson snJ west, 19Set. e:pe.r
"un:el r:cte:r ~Janes. 19451. Ce;.re:enrt :Csuren nd Cark. l9+)).
.1ram:n 8, Je.1:C:enci, (S.h~srt:rssn snd St:suss. lia9), 8., reouvemenrs
-S:ne:d e! aJ . 195)) .
For ser^e re]sons. -*hl:h ]re h]-d !o "vns:ers hast acqulrtd a
re?u;a::on as "vt;tois." :o ^3~.~a." "'JJr Sret:ers," "subject to ]!I
sor:s ci ,;,sc]ses. s..;` as :te m. sten,,;s 'Net ~]:I.' "";]rntrs of viral diseases,
:.`.:eate.^.:ng :o -:n." t:;. On t~:e :;ntrarv, ur _wn experan;e, g]Ined in
5:::~:es :c%oi::nz :!scus]r;s :r i]ms:e:s jrd :]:t^g ?ro^t :QS', has shown our
:!esed ;olonv :o ;.,ntut >f gentle. e]s:'v rar. :eJ ]cim:iis breeding at a ractd
r3:e. %3r:]c:e ]-:-: ^r:~ str,::s. .:t n ]~r.]3tng ye!I J~er sesen
;i'sp rL^g xes-e_' er '.:!tr, w::h -anv t n]as :emalntr.g rtt!t 'or !ong
:.^!e. .r:e JI :.Se]st :f ].eC'.ua!t!v ^.rpltCrtJ 'rC^7 ];;:.~.en:3J
S..S;e::t°it tJ miny txrtr:r^enlai ::1:ectlons, Irte Ot spon
:ar.eous ^e~::`]sr.s. ,ec ~,;;:,;y sus;epttble to :`e:n:;y carc:notenes:s, ]nd free
_r ]n::.c.;:es ].3:^st :noKn :cdent and hum3n aruses texce,^t for ]ntiboCies
]1a:-.st : r,aes :o +`:::n :rcv are o;caslonally :a:e:esslv txposed).
SPECIAL CHARACTERISTICS OF HAHSTERS
In addit:on to these qualrficatrons as an ex;ellent Iaboratory 3ntmal-
'3cic:-g, it is true, a handy tatl. but also devoid of the obnotitous odors of rats
ind mtce-hunsters have special characteristics :hat :nake them suitable for
s:::,es not feasible in other animals. These properties rnclude the :heek
an :deal site for transplantation experurents. It is easily evtrted under
1:g;zt ]nesthcsta and tnc:sed, tr]nsp!ants (organ parttcles. cell suspenstons, etc.)
are :ead:l,v inserted through small puncture wounds or by means of large
neeC:es. The tra)splants are observable by either evertrng the pouch perr
od,:ally for tr,spe:tlon, or by tnsertrng permanently a transparent window in
the skin over!ying the pouch (Greenblatt, 19'1]) The cheek pouch of S>nan
hunsters has been used *or both homotransplants tHandler, 1968) and he:ero
transplants, es;ecully of neoplastrc tissue [such is, for t%imple human tumor
:lssues (TJoi]n, i 959)j . In the latter case. Immunosuppresston with cortisone
suf fices for longtum sunlvaJ of tumor tissue. Nor-r)al har;::r organs ;an be
CTR NN 0422647"
38
grown for long periods of time in :heek pouches of .,ntseaud himsters ir.d
remain functtonal, as has been shown for krdney (Caeeablatt. 19':) ind ^eart
(Handler, 1972; Handler and Laird 1975), and morpnoloatcaiiy :ntact. u..n
the case of transplanu of hamster Iaryngeal rings (Homburger et a).. 19'Sa).
Through the use of inbred lines of Syrian hamsters. Handier has r::ent'v
clarified hastocompattbtlity mechanisms by means of skin transplants tH3n;'er
and Cosman, 1973. 1974). He confirmed the paucity of "strong" :r3r.splar.t3
tton antigens in inbred hamsters previously noted by Bailtngham ind H,:ce
mann (1958), but reaffrrmtd that the capacity of the hamster to re;e:t a
homograft confronting it with even a single "strong foreign" trans;.iantatron
antigen is just as well developed as in other mammals..
In light of these observations, it is necessary to reevaluate ;heek pc.,:'t
transplantation studies employing inbred lines. The Syrian harns:er ;r.e:ic
pouch system obviously has a great. as yet unexploited. potentrzl .'.)r ::Y.;
cologic studies in sinr, in vivo by applying noxious agents to tissues in cheek pouches under little
systemic influence and accessible to mrc:es::: :
inspection whrle alive and functtontng, to recording of acuon :.,r:er:;s. :H
changes, etc., and to serul biopsies.
The tlank organ. or scent gland. is another attribute hamster. Its function is not fully known, but
is probably re'X.e,; ~) ~e%_L
attracuon and.or site marking by thu terrstortally ^,osuss:~e 1n:nai 7-c
reoon of the f)ank organ ts characterued by the presen:e of seta:e_;&s ;.ir.,:s
th3t in the male are darkly prgmented as a secondar. ser :^a:a:tens;:: L.d
hairs that, espec:ally tn males, are more black and b;tstiy than ::.ose ;( _.e
surroundrng skin.
T':e response of the male hamster k:dney to es;r"cn w,th :`e fcr-.a;:;n
of :enal cancer is another attribute of this species that a^,pears to be u-:: ' ..e
X:icr.an. 197:). T'.rs system not only furnishes a model of :i
h4man kidney can:er. but it charsttert:ed duthylstrl5estrof -'DESi ss 3:s:
::r:cgen long tiefore cbservauons :n :aaa,h:ers of mothers ».:- s:..xs
trol .4urtng pregnancy revealed that :hrs substan.e (DES) :s a:i:: .c,e^ r.
..c:mans (DrrnKwater. l9"4. Mtlls 1974).
INBRED LINES OF HAMSTERS
Since 1957 a number of inbred strains of S.nan hamsters ^aNe ^een
developed in our laboratory The :' ;nbred Lnes (:0 _r :^.re ie-erva;,r:s ~:*
brother X sister mating) avatlable todayr are the result of genettc s:'JJes
by R. w'Mtney. W C. Ntxon and C H. Yoon. l'nea these tr;i:l :n.red
had been available, most leneuc stulies on haTsters naJ to ^e :srr:e ::
.vtth anunals from "closed colontes' or Mith soca:led "wearc:y s:-a:ns "
These studies were sumrnarued by Robinson (1968). On.y ".+r,en a s;e::es
' TELaCO. Bu Harbor Mune 04609.
CTR NN 0402-648
Ihimrre. C'ie in furue 39
has attained the rank of an inbred labot3torv spectes ..."(Yerpr.tan, 19
do reliable and reprodu;tble genetic tn.estt¢attons become ieasr5le. Ltmrttng
himself to the _' :nbred lines uf Syrian h3rnsters urrently m3rntatned by the
B:oResear,h Institute, Cambrtdce. %tass3cltusetts. Youn r 19'3) has described
tFe Pe'Iet::s of :b Si\!.'tn J( :hese :nvC!%e :OJt ;O10r. rlv[ 7:!e,~t
Cle n3t'Jr[ of t~e iJr. tJUr Jre nr-rc,:,:aiC ianc,ntluirr.;3. htcJ'eg ;Jr]l)sls
h, ,'.roce-h3!us. ;etz-ves), jed unc j:'c.:s :he s,?:?t.-l 3nJ n:us".s.
LairJ ( t9'31 hat surunar;ze.l t!.c uics ri iorr.e :n^r:J h3:rtsrers in pharma
ar.i In ac 1_.e es.nbeJ :er._enttJl
s:e:;al sus:e:.....n:s u! ...ti,n ;ntrez n.r.u:er i:ra:-rs tJ'1o\:ous 3:ents. and
.na !;as `.ed to the s:u% of .nc r..a;~.amins it i:,n,e ., t"cse itr~tnspec: i;
SJSarL'SI :L'[S. .a' ~.^._ :`[s.' ^'er:,2^C.'1] J'? 'e S_i::~Y~t lt\ Jt hir^s:.r5 to
t^..:~Orr:~[ :R t....s :' ,:j^/JJJ.:J ^~ JrJ: 3.,"ir.is:ratWn -J(
~'rU2 I: A:i S.':., _^~_... . 'I:Jt :here 'atr. i;._.^s 3'1~
::.'ter.
of
t~e %:si:. . r? n ;rdt.'.i; ^]TI
s'.rs .-.3n .,. .`.._..caroons Kere
-e ntre ,^?s ,. 310 ^.J-'s .S (t.]r. .,, Jl.^.ea
T`, II :nc, -. I .^,:, 810 `.-,ste!s
- ,- _ _ . ... . %1C i. ,en; t i -. ,re BP+. ~: .: _ . . ~e-.ur, ra:ene
3A t t: r:..c i: .:sc _3v e :at:s ,i r.-.or :evei:prrier.t and total
:nes '.r al! .~.te
-5 .:s,,,, .i.n.: s.Jw J^J :QA :'1 other l:re5 7~e 3:l:j1v reT; on.,:n¢
z.,. .,.. ts..s;ept:ti[ or ft~:st.nt onesl M[r[ eSSe'1:,~, ~:.`'.[
s1C", .., .'.e tr .. : ,r.t !?Sr; J. in 1:! ,]seS. :~e :umJr
::sT::se oi _. _ Tcr?J inrnials v.as ;nterr:e,:;Jte. D%1BA »as the strunlest
.ar::nogen, followed hv MC, BP was the weakest (Humbur¢er 19723. Horn
bur:er et aJ., 19":b) (Ftgs. 1-3). When N1C Mas aJrruristered by gavaze to
`:-3:es ui st\ ;^6-,red 8I0 stratns. a number of neuo:,uins Jeve!ooeJ in vartuus
r..ans tH.-tu?er and Hsueh, 19?l). %tost sever[:y Ji~e:red .vis the mJm
Tan iind. T^e randombred animals stu.,teJ and one oi the inbred Itnes
(BIO shov.ed a relatively low :nctden;e oi :_-c Jnd 61'%, respectively.
wh:;!t was not s:gntricantly d:fferent from the 14 5: ut,tJen:e reported by
Deila Por:a ( 1961 ) in a sunilar etpertment on nonrnbred hamsters. The
.-^,a;ntce tn~rel ltnes t B10 a~_, 14 16. and 51.') ill showed
marr.rrurv tumor ;n,,Jences approuhin¢ 100"c ITable :1.
Lttle tnior^ auon cJn ~,e found in t`,e I::erature on tottctty studies
:^volv;ng SvFtan hamsters. and must, rt not all, puc'aheJ stuJres have been
.icre wtth ::indom~re! 3nt^t.tls and. Jre not re;!o. :;:~'e
Our uwn s:.ctes on :he LD<, oi ni;,;:;ne tJrtrJte 5~ tlic :ntraperitoneal
t:pl reute :evea:eJ ::ta: the:e are TameJ i;e;tes Ji'i[en;es _mun¢ mtce :1ts.
ar :hamst[rs K::h ;!:e Svr,3n hamster bv :Jr :!~e ;^c!, resistant of
t..r f R HN 04~...".. 6"g" 9
a
40 F ~
% ..e.
c CtKt
OC~
/
Kr- ~
~
s; r /
/
sc~ ~
o- i : 1Y U'
~ i ~7
~
sa- ~
sc st . y .
fIGIRE I Tursor de.elopment in !he s-jPcut3ncous tr"je'
SJ ~.e of drmc:h%ltrni3nthr3:cu rD%1BA1 in rnDred snC :nc :u of S>r,3r h3rrmaters. T9t ntdrum
wli tnca^,r% Irn rE.--.]n A:s:
I-.-:wn sr.es .ee ;lipsteJ ~recly End r~.nr nrred '., i.ese ! .._. r. :e-_.
.".lt esen:u311. ~As co tacced I . . _ :.z-:e: .is i:s:
L't r110 15 16 !t'; en:s ucr.r;i;~nlly rrsort .,n -:s: ..-e
:!e 3mo^,t ~I,+est rts:crJts. is yere N10 1 5 `j-::es : 1,':
re s::;r:,rt :f :"e :.1ket ;::: ^ cr.s esa' Ke;n:+e] *:a :e-:ss::r _ ~:e
o; P%::.'recol:,Vc:i :7C
:S] ._,;rtS µ~le^ th.t feSiS:Jna :0 :i_a3ret:e S'Cw: '~3S -.'75_!_
7:5 ln,'. 'i'1s'.'S. !he I]tter rr0%e1 r..... S, ...;1.".t
!,,i.Ol:ne t7rtr7te ip 7nd STor.t ]!1L: , ..-- -_
': ^e:MCCn ;;;ant strllas Jt S%rl3n harns:ers tBerr;ei.'
-e,Fants^,s oi a,;h cti.. ,._:s .. _ -...., _ _
.:e s]me S;e.:ts s to -.. ._-
~^ + , :5c_ ,. t0 toxic sL~stJ".es 7'.J, !cw :r _5.,. .....
so _
T>.. ,K :i F:lji^tan ., 7L I:a'il .+r. ..,..,n . .
S I .,^.te:S! ]'. ']\, ' -otrt in ] .. :.`s ]'°d T'',e,
-gAPt
-S. 1;tJ 'r7.. tls R'3r;Str^ed rn J [] 1 . . :.s ]ite,
F:Us .r~,re ir ;cettrneJ !t^ BaP I:.
~. .,res ai :e 910 15 16 str3tn ihoMeJ 7n e.e% 3tc~l :cet
t::3r't,r9t. in :7nt:]S1 tC .. . !S_ 'S
'-:n r]n.lortorsd .trJ the BIO 87 :0 st:]tn of h7:rstcrs S:r:e . tit
r,:nts M:e ior,e rt has heen r;portcd ~> us
lr.ntt oi BIO :5 16 rs slgntti;]ntn more s.:s:crtrDle :o
l..r f i`'~'. Hf'"{ 042650
/ b
/ ~
I 7: .. :.
.~e . . . ..
e . . . . .
,~~ . .
.. ~ : q.
.~ ~I .
_ ~ . . . .
6:-
.__
X-
:>
'~ ~ -- ----
:.s
I!_~ s:e C sr .) ::._r r T rc:k vf r,
-.~---~~ - - - - - - - -
.. f. .. . . .. .: .! . . .: 9 1 K ~'
flrlRE. ... .. nVr -. . .. .
-. . e ..-e e.^.rnanI :r::e'
1t./ r1 ../:G. : ( . .<.w...
J1
FIGI RE 3 I.Inele ` -K,r-n ,,1 tn0 t
t,rrO tlJ..nj .,r.InJCIn 1.IIn
':Ste IJ )ilrr ~ 'jr- .l 1rt...:1.e ('., Int '':J.ncr Ir1 J7"J~ .~ 1.k III1l) * 1g J :4 (1~ U.
'~ .6. 11 ik..,....I 'I nrC'..'. li^.ri. V!/ .IJ IIIQ I!..ilm~l{
lcis , ... '.C r.url,l :r.i::n.: .n .n, . .Im
.... -.a:e . n . . R.. :,ie,1 . . . -c . oSl,.n .. 76, 8- .rllq . v..iel.ol
..1 t n. :i) P::mor.7l S-7t
CTR HN 0422GE51
n /. ./ / i,. ..,in ~ . .
'L 7
~
/N t li .11 il i1 ~ 1; 11 11 11; (N
IIN i 1 ,:/~ t u 1 L .i NI f 1 `
If',N
( N N N1 ~
r ~
. N, 1 I ,a/i ' i iv' llr 1 f i N
/.v ur 1
1/. .:t MI 1: 11 .~1 ;1 ti 1~ 11 ( rt
ur .i ,Ali t) ~inw
'IN I 1i 1/ .; 1 1 r /i . I 1 t '1
v 1~ I ' ~
/.11t, ,.f.l /1 1/1 1 i 1/ i t I
!/.1 (1 1/1 ,.St t ,.\i NI N1 \1 t ;i I
(1 /11i i i I1 1
,:~
li
,nS
cL
~L
o
pr1
li
/t Ir
~'
IIM 4iG.
11 /1 O U t 1 1 r I t 1. ~.~/.
i
UI
6
`I
11
n
/f.
nr i.
.
( 1 4J
Iw.rla .ull1,1 111q1 .u11'/1U1 .ull'lul /1.luIC y..u..l .n.nu.% "
I.1u. .% uu.l\
q r.u.ur1Y !Ir I IP mC ,.. 1 1.. N ,r . p. ..n N
lo wwno/.Ir. ypm %Irunur 1.
.P.ni :ryl I~ q.l.Lya(I ./rul... 1/1~ au. w..ll. 1. nwn. 1 pnw 4p I~ q,... p.uu.V p 1- 1
u i~ '~4 L/ 111\' (
,
a
H:mr:er C'tc :n fut:ie Tat:: 43
car:^acenesa than that of BIO 8".:0 animals Hen;e. :t m:~\ ~e .on;!uJcJ
that :~,e level oi btn.rng Ktthout rnductwn (b> .jr;:nocen lJmrnrstrnt:on ,n
s:r,;, o't.r to ..;:tur:) is :,oIt!> 1e!jted w'iu .:r::.a; n:hlt
de:errr.,rrs sus;err.t:'it~ :o ;]r;ino;enci:s.
SPECIAL l'SES OF PECI:LIaR INBRED HaMSTER
SI.SCEPTIBILITIES
S,tfety Testrng of Crcvette Smoke
: . w:.. ...
e\:.. _. . ... . . . .._ 'i .. . . ._.J:~_ . . ._.:~ ... ~ ._~J . _ . . ..
N: .._. . _ _
....._.-... ' .:'_. _ 1 ' ' _ ..^.\ ... .. " .. . ..._ , , ii) . ..
- .. 1. . '~ . t ~. .. ..! ..._ ..~.. _.. :D:i..~ . _ !~: E.1i... -... . .J
.,-.. ' ~ \ . . . . _. 7.Q .. . .,. e c '. l'.-'
. . -. _.. _._ . .\'... -. 'S'..i .~ ...:~: ~ . .S . . .'t' . ' .~.
.. . . \'. . .... ~.'~.~ . . .. .. . : . .:) J: d ":.
t- . " _. . .. .+ ... .~.. . . .. J: . ~ _.~ . , ' .
,. :.c :~~:~... ._ ~.\ ~~~"~:.'s JI 'C .."e . . _ _.S j!.
:!. ^ _. . T . i' ~; . _. .e^.. ~ .. . _ . .. ' -t J". ~ o
... .. ._. . - ... . i :\~.a..e +.i . , n r,\: ..):.. ^ .
/1
, _.-', I , , i A_. _ ..+.~e~ ~\ .., fC. v: ... . .,. J~.'1 .. Jf.~
^ I~ulume w`]s pushed thrJuelt vte .:;Jre::es T'e
as:.l t . . ~ r.ornrnt a-J S rntn e%,cry :'.no,,n %e - .,... : !
.71.s c: !__:t +e!K The cir:)on t11JnJUde s.,tjrj1:.n 1:1; ,:
c, 1~el - c\.owre (_0 mtnl N]s up to -+v= Mher,]s :i e:.: ~:',.ne .
iC~e:s Ji 0 _ _ 0(7%i.'Jie. 'J 03 r
T':S rrv:e6'.+re drd not ]:le.t the m,:ttj;rt\ ur%es ..t 1G: e\~-:Se.
,-.1.^..S:e's : )in itrlt.^.s :hit N::e superlm..:i:-'C :J ':vsC . ~el rn t,0
(7ne'eJrn1 1:1 ntJ~h7ne :,tJni, u;Jt,vrls .r:J
re:'esr i'S C~J 1'!:r^l;s rC['Jtcrnlf !n t;terr .lc':s +:J::::
!,e:ng r.an I:eC e\. . ijr ;]ge '1:nnces r1.tuJliy. i::e s+t:'s: ~rtr,.`J ~''~e a
.J'1 . .,:i< .;Qt !\oJS.J t,etltv~: 1
T~e 1nIn:J.i J1 t~e Bl0 D -'0 ilne 'I.Jt i'T1Jies J:_ ,. .. .. ~.e '~:'s
0, .... S]Te ..^.C L1 :+: .n2 .a!:. :t T~:s y.Je
.t:e BIO i5 !h :n!
CTRMN 04"653
44
e ]c;irm:r]r,cns in ,-e BIO
. ,.
w,s ;ss ; r.mounc: r, te BIO I t;c
~I . . :Ilu i! 00 J.I ...'f ... . ~. . . ~ . ..
J: ~:S Jr t;.zr ,ro5;i% J^n.rt1Jl .)t:j',S we:, ;:J,,.t,:
.~.
sJ:'.^i:t _^52:~J::~'I!S wCre an 11;tJtn.c r! S(rr of ;h]!;_cs in thc BIO I5.lo animals. w,:h :0
It1-aSi%e :r,.ncc]:
,_rcs,or:d:n; In;IJcnces oi epttheltal ch]ntcs ]nd ;]n;e: .., .ce 3:0
~'..) anln:]is. In the shamsmoked and .aeehelzi cent:ois. no :: r:e];
Jrom,Jl!ts were sccn. In addition. thcre wcre two nisophar%n;~]: -].'y :rt
tur^rs in !hc IS 16 StrJ!n ]r:mais /unt. 3 sat.om] wim
tasesj and three obstuuctt%e tracheal paptltom.is. In the BIO 6- :0
;hcre wcre iour :arce sn;heal ,^ar Iflom]s It has Secn s"%NA-n `t ::::
that the !nh]latlon of .!carette snioke :auses lar1 r.Pe]1 nc.~;.]s.-s -- S %5-
lumsters and that this respnnse is except,ona;l. strorg :n BIO
mu:h less marked in BIO 87.:0 animals. and also onl,- Inoder:': .^
6rc.1 antmals. In tl;e same Issuc ni the Jnun:;r! ,>j r%tc
lrtsritulc. µ}rdcr and his ;ruup ?ub:,shcd s:mtl]r v^sc:%a;;crs : . _ .
Ae 1.1 :]n,;u:-i-brcJ hJ,ns:crs as a :OcV;inj:en "or
.;d i]nng:]I tKoo]%]sht :t ]i . :J-31. ,
tr.J; Dactcn.1G's Jnd :ur -.+%.n croer,r,ents are ne: .: ';r_- _-..,_-_ -
L.~.jr:c5 5:::h as II'e 7i:Icrcnt :1:]re11CS ]:1d e..,.. S.'.^.., ~, "J. .. .. _..,.
-i r+dl.i .wi :h]t . lc s:r]:n :n
.]:n :7r%es. 3n r']C:,):r1]ai
......e.: .nJCr :C:^paraDle CJnt::..,ed Jn.. ... S.. ....,....
Studies on \13mmarv Cancer
I :_.!,oit .,f r.]rlr^a r. .]r.,. :~ \1C :].a: nas j ..- -tr.
:J ]CJ: ]re rC S7:`iC;: n SJ;Te _.._.. .._._.. .. :].
Cte;ts ']r . :. +
~'e On .:`!cGU]: :r,worntG:]. S
_ ...a-.and D, ;] P. :3 ! i,a-i 1 .se-' _3%j: ., ] s. - - ;C
.^ree Ur1eS ] w;±k 'C' w~ . . ..- . ~
.... ' . i
%i C ::. ^.ar^.S'tr .^ 7 ..,tl;.':i
. _--~ .~..... k-..
].', ,r:,,~.e':e .: :1.-
`-
';
, . rc ,.!, .:c ..nc, tB10 1 :J-.:~
ti10 5 ' _','. . -, ~: '3. ]r.J S6 4_
1' :St .'1^.:S :];; ne a:ee :a: _ :e5 '
.c ~:.;c .\. _mrn]n ]_tnom] .,^e B. -]
C. ''.oro] ~nJm]t ,%:!h t~,es a and B :' r._ A - -
Dunn notes that i.rnphau: metastases are ettrc:ne:: r3e ln :-..,. .:ie
,,Jr irctiuen;;% n h]n,s:ers ,n tr¢u:ral and av;;]'\ no1:s. _' . .
sit, 01 :he ;,,rnor P,,;mJnary net]s;ases ].so :....:r c_... ... a-'
1
C T R H N 0 42- 6 E5 4
/1
!fJrnlttr C'st :n futurr T 45
In these respe;ts, the tenwtor of N1Cindu.ed mw,,;n3n ,an;ers cf certain
tnbreJ hamsters resetnoies that ot hunlJn bre,tst ci%er mu~h mure c!ust!y
t!;an murine n;3mmr. ;3r,:c:s. Studies on the !tormome Jependence of su,:h
tnduced h3mster tumors in our I3qorvJtlcs h]« shoMn that tne o%3rv ts
essentl]! (cr h.1Ts'ers :J ~c S::S:ep.:Dle to 'hls 'Jr^1 ot ~]rCtnu.eneits. Sp3>eJ
:rtJ'es ...:.~. :C jC~C.... T:]^ ^'J: .J^;er. ~%Cn ~%^.. ~~C^ :]:tnlc']l es:rJ.!r1
STLDIES ON THE GASTROI%TESTI.N>L TRACT
In I.:s !0-1 %!.u-Ie a^5,':t Le.:ur; ar et~er ^en;3.;y ;~,t:ctd a3strte
^i.':
..... ...met. !~ \ -'71trJ\'.ri'., i_ ..:.^.._ ^.t. ]nd Ht'3R1
li~~:l _..., ~.... .:S .... ...... ~) .~ . , e:.-... r: ~: ~1
~~1"'S:.ri ....:e ...... . . _ . .~. :.~.~ .'J 11... .: I!C..J1. _S;nQ
. J°- i .~ :^e i..J!t
. :C i, ..J ^ . . jtcer
_ J'.. . J-, ,. ' . . ~t .I n.. ;1ntteJ
~- . . . 'Il . . ]. . .^C
..- '--. ,i;. ._ _. .- ...
3' .!.,e S'.~ :^ 'a T.SIer, S
~ :.. :J .. ... . , . ... J' _tr _. L~ ..
.,1 n..rt ~,. ... i;._.°.i v..,S C
~~-.- . i:__... ' . . ... . :::1et., r.J
\1C :J::1i I M~
.,. ~e T-.cre J. m;,Ji.lne iJ;turs. iu:h J> >cv
I , _ _. . .~em ^red :n:m3!s ~.here I; m:ies Jn,: .1 'eT:les sur.lved
-i a ! tu _ .. r; :r.d wVe ]utOpsIeJ. en!. t:Ie 'e -sJ:es ;t:J (:I Jncers
.^.:rs. 1.3'c. sm311 untesttn:l tumers. .n ;t,er. :c-
i'.S IJ !he e3r!:eT U;`scr%JUons oi DL*J Pjr:j t I`+7: 1:n Irtcs!:n3!
:n r.onlntred ]nrma!s b, the s.tme reelr.,en Pc
.:^a :es ~: s0er]1 of !ne inbred stc3tns SFo..eJ wmiIJv) GI tumur
.,:er;es (BI0 I: to. 4s 7, b. '?. S6 9), ]nd e7 :0. t'te BIO 67 :0 strain
^3: ??' tur-..;rs. hJweverl On the ot!,er h3nJ. :!+e ieTJles ut the BIO
a:: ltr.e ShJueJ t:' s:r.:a intesttnJl tumors as Jirc3.1) nJ:eJ. noninbred
^:3 es r3J :tu GI ~Jr-,,s T!te r^J!es of the BIO F: -3 .tne :iso hJd Jn!y S^r
r]s:., Jr.J s-n3!I irte,ttrJl ...:nors JnJ :'YT ;uiun :uvnors
In eer:e31 BIO 5: -3. en a3. Jnd :; - 1:nes situMeJ ies:s:]r:.e to the
C~ve:opment Ui GI In ],1 .t the ~,ther te.reJ ':nes it lcrst one set:ment
lut s~.Jwed an N1C.r,,...eC turnvr ...:n;e 3:oro:..^,tr3 :n- B10 3::.
i"1l;: tn:es:.":: :]n... :n .;.~ . Ji ..:e fT1].es _nJ 4t a Ji Ihe 1eT.J.es. 3^J :J!Jn
C T R I- I N 0 4 ~~~~
I
a
46
. I
~S1J .. .. .. _ ..
:JnCer ';1 : J-Jt ^']ie5 ].'.d :o :]n:e' 1 l5
810 'k- _0.
!n ' r J::s r::mJ'ts ?n:. :]_.. -.it ._r...rsl .. . ..
.`I r:] :s
TI'e 'wCp]1'!.IIL!c t u/ t!1C %1C :n,;t..:J e'. _ .nt..
:!.e . Ivt~l: Ct Ot I:J'.t]rl C]n:c Th,sC
r,. J:s. !i!Jnt ."et]s:]scs Mert .u^J :n ]r.J :~r.s` T!;e a;,,-.
:urnors.jre reJJ!k tra^sp!3ntable into il]mster aletK Pou::;;i
1]r)
STlD1ES ON SLBCI'TaNEOLS S.aRC0M4 I\DLCTION
IN INBRED STR>INS OF SYRIA*% HaMSTERS
T'e a1lCllc J.I1Crcn;ts !hJ: .iCtCrt'':nc '!le
i!rJe Jascs '11' rul.:y"1: n% ort/:]rbnn .Jr:cn,icens n . ^ J S:
`.:~%c :'ccn :rcct!uncJ ];iJ ;lustr]:cd ]hu%e T!.c
!mt.:!on st::t jf , oltct;!1: ht Jroc]:`'lns ]rcJ :1
resJ!l c;.n~rns cn t!lc :n^r,d scr]:n rl,d ;n some s:-.,.r.s ... .. s:~ .
~ .. ... . ' _ ~) ' ...
in .'.t . .1s: s..s.:;:.-!l' s:r]1!1 :.JJ r. %IC
]'1 :0 +~ T' e ,JSi tiiS:]'t slr]tn e\: :~I:eJ ._' .:S ;n .. .. . _ ~ .. =.t
~.'1~,^.1]It J( JV K
Su%.t^,^. .'~r:J S,;jn .]:nSC,-s ~;ciJ s. _ '.s .)' -J- -
, _ T'e ,1 . :s :; t. : ) _ t .. .~ .
BJ.Ct IQ0'll Ft\a JJe'.. J+ J' ]:.. .._.. .. -...
c - :.._
. e' .. .S "_ .. . . -
" .. t! R \A
" :tJt. . . J _. 'S Ir :r7 :1 ;+,:%... .:_. .. ' . . .. - .
. , r S itS ]'.. .t.e ]t, h.]. ' . .' -. . . .._ .
~.c . ]n .n.
. ..'.~ L]~ .. 'S . : iit' .'l
)TLUIES 0\ I\ULCT10\ OF C>\CER OF THE LRi\aRl
kfLaUDER 1\ H>%1STERS
...-..~ . c . 'Ji .. ~ . t._, .. -_ -
,J C ~ t . . . _ .. . :; '
S - i) "Jt,J '+ . ._'a . !1 .i^C' C' .
,,~ att tS :n. ri1 'J . i .ti .. ..
:s J' :r
~jJ ~.., ,..-, . n tu
I I,JI,t ti JI (!'rrI) .):sctl,.J '!,Jt ']~ ..: ..... . __.
.Ji,'er .1 1,e .,:i;J'V F)IJJJct In `(Y: t ,IVnI:....,J S ]r~ '.J i-.t ~,
9 .II!1 'It %J'ti .
J:"we n . .. :1c1 rJs F1]rn.iess.
CTR I-IN 042"GE56
ll:^:1:e C'tr .^ fur:.': TT:,+ i:
I
than ?0 c Ji the suw~os (S7itiutu ef I! Thrs Hork wJs JISJ
ccnJuc:;: Nt:h n:n:.^.trrJ h7rnit:rs
ln:ii noK. no :rin7r% hl7J,:zr c7n.ers h.r.e teen orcJ-j:cJ ;n r7ts or
n;.. rt '!le .'J. oI .Jr.;GV::nS J'.: ~^Jer (:7r7SjtCI::;:
^i!It'ti :! Jt .,A t.^n fJIS
'S
.... ~F^ e: % :~ .~_se_ r:s
T a _J\ ,
~__,
_..".,...,.. 1 , ' _ '. ._ . ,.. .. ... . ._~ ._ . __tii ti
....^a'.
,:i ._ . .. 'S e w,.,
$_.... , ~ . . .. . . : ... iC. _. i. w .. . . . ii . 2
..
T .. S
... ._ ' . _.:5 ~ , :S1 . :.. .' ' .> >_-i, i
y..,'
INCIDENCE OF SP0'%T4\EOLS NEOPL>SMS
IN SYRI>N H>MSTERS
STIDIES 0N THE INDlCTIO% OF RE% %L
M(,+I': >S%IS IN S) RI>~ H 0tSTERS
\:f:.J!
T'
,j~ JeJ'ing wl:n SpJn:7ne'uS n 1\Jn .^+Sti'S
.~.75 ^e: . _.. _ ., _ .. .!S JI nUn+e::ne.t I S ^~M
~ ~ :s: SD^ctJneOUi ne~ci7,'1i vt he (:7n+src-, t.^7t .t ~ ~
R, i,:..'J. 4JIv it S .'.J :Jt , ni: l~rtJ w^++'J
'_'i i'e . .. tJ :v "J!1) Jr:,,^.If,ji:J!'i[ I.) p:fii::l Jr1y %un..u
_'r to ~06:. in w.^.t:h F:iri,m7n ,JnJ A!L:7rJ SJs.J 'hcir
w.i.... J:
F...'rf'i
i
~
C T R M N 0 4 2- 6 Ezz iI
OG.,7ZVO NW ~110
. 1 . ^_...' \
-e
% >'..r-
I . _ . ~.-. (
a19\1
.. l.;
~:C U:C!C fir.. ... ..~. ~
... .. . .. = r . _. .. r. S;C;. _C - I Ut S.:SrI.. a,. 1'.T . 1 r , r,. .
_ .C?. ,:r. . . ..C'_.__... ,. iJa a:a~il ..C SE t;r ;Jr ....i
_... ail s:ra.. :r.:, c a :~. ..
i J^.. ..1 ur i,. ^ . .:,; . .. .. + ..r ..
.
. _ . . . ... ,..:r F.JC. SI llv:.C.UJ.`. Jt) l:;r; S. ... J_ ... .
1r.i, s:.. :.r
,. ..
J..I:I::tl ,-uC UI U:?uf1.` ou 1" \;SI-~1w~'
U: a?uarL`Ut JC`lC^1 SrJJUCJUJ.'t.S i121Ci a:;l fi5
_ s;_:,c asa.,l io ascasl; a,llclaua8ap snollnblqr lsoy a41
I:a l I sqGk'H Pu_
SJ:S.::Cy pJJG:au()U .10 Suct'sa;
5' . i:..°...f:. , .U. 1.. lilr' V1Pa ,la,^.r;:: ?C: IC+ S'snC.'
\; .. ,. '1 ~::61 ~a3Jrow,,~l I s!a^ .u: ascoi ; c: t:Jat~ul y:s
.: ic i: puri:au!!I s<r^ tr, .£-
.'. Jy;a p?,q-IIoIjS ISJW Jql S% cr jhi 1c' 1n+I:C,a~
0: _~ 019 ut u: iE.uvri urJ;u.ISJ:uo; .yl
nr, ~ r n:3:Gr J'L)aUllllr\, s.ul; f+JJy01 ; l :uPtla
'.. _ _.. wn^'1S ,:a, ?vC ur S S,tll .. a`r Ir, Sic^
~ SJ'C'Ual p::r 51ih:: ~ I.. u' f Ilr 1_(-s1 Gr:yl
70 JCa \ IS::L a4: :al. C aSCJ:.`7I
UI .:1 t0' UM.t
. _ _.. .... r~ ,.. .. ... C' iJ+JaP1` 5f;.._
sr
I
1
1 , '
/famsrer ute rn !u:Jr g. 49
hamsters. His sear;h. br ele:tron microscopy. or such .irus paru,ics in BIO
!:omsters has so i3r beer. ce¢atrve. T!:e I%mphorr,3toi,s in Europe]n hsn:ster
coion;es re.atis the 1058 report oi Lt!!dt nn I>n:,^horn]s of S.r!Jn
hin'.S:C's in Sw;tl:rl]CJ It is tuitc pUSSIh!c :f']t :!.e5c Lur^:i,:JC ;nlur::,~s ,(
S:.:J.^. ']'T1se.'s Jr !nte:ted »-Ih J'l. .,.
Eur,`,-e]n ].^.J L.S ;viJnies Jr S~r:]!1 :1J^)S:e!S iui:iSt J) :!
:c^'^e,:.'2 ]nJ .]rc':,11 prl>t:.,.on -Jt !:JrSie' rc).
'^ 5.^:IC :! . 70!.. V% :e C %:r.i IS:c^OJ.1. eI J; .
aPPLICaT10% OF THE ABO\ E OBSER% kTIO%S
TO SAFET1 E% >LLATIONS
, ,J.
. _-.
. ',J^ ..:~ ._ .. \.... f ... . ~ . '^ , .. ....
_.. .! .. . . ..:K _. .) J ' .. 'I _- _ .
. .~ . :A . .. .. ). _. . _ . . .> ,. C ..~.... ~'
,....5.. ._ ...~. . )'.._.:1 .. ;^~. .. .. ~J .. ~JT. . :S
. _.~. ... l,~ _ ..... ~J. . ~hJr.^.1],CU'..JI . ..'^I,. S 'A. !1 :J:r J ....
. , . . . . _ .. ) . . . . : S
. . .. . . .. .. ~J: \JA .'.Jt . ...~ ,.r.;i 3e . . .61 ie . ..
r,^s I' ::.ts »ere the c3se. then e]msters "c .,se.! ]i, Jn
.._ .'rJ' s=e;:cs. .)r e~en the spe;,es uf ;'J,:e iar :;srs F,,r
:~e^ thouv,h it has been Me,I knu»n s,r.e flr;~~ 's »ori; in :he
: is ]'J :'-0s that rats Jre unsuitable !Jr :"c tcst,ng "i .,rr-.]r. !+!]J!cr
;3r,'r. .,^.s tc:]use of their sus:epub,l!:. tu !!rc u^,,:J!:uus Trn n,s,,~,,
c u.:j »ork on ;arc!noeencs,s oi ;,.;I]mJtes is );,II rr n,t pusucJ in rJts.
ex:e:t i.,r s,!^.e unp-ibl,shed nce]we hamster stuJ,cs by Sl,ub,k Ob%wusl*,
:~tt »Juid be Jn (nren~t%e ,nt:dh.i!iitn ituJ% ui ;,~c!]n:Jtcs :n
:ntre.' .`.Jns!ers, wht:h are kr,)»n ae.er lo j,:elup spo!!t]neuus
.]^.e! ]r.,: J;e sus.ept:'i: to :iJJJer ,Jr... :r,1u;twn ^.
J.^.J v"]^ino]lOtJIJe^e l^.Iess ':'e,,r.,es were f,,und
w .\,.iJnljtc in If]r15::!s Jr :n . 'IJrS ] -J%
1! 3 'et,',:r1 )tuJY KJu!J then .^.rc~iJe J.:c'1mtt\e .~'tiwer to J%e\!ne
T^:s ,s. t,:c Jf J,{ potctt!JI ur!nv% `J Jcr :3r:.^.JC:'1s :(
th.e :~^C iJ01 J'JunJ »,th JJes :Jr :n :J'^Sle'S Jt t!tt
,tpcroprlate s'!J:n »;'! ? rp%lde 'f:c JnsNcr in J5-b0 +k'
C` T R N N 0 422 6 5 9
50
S: J^'K t :1 nt+ttJ :irat " the ~,i _ ..:s
s'jJ,:s :s ^]stJ u;on ; rlor e\;t:tcn:e. :r tc . J:-.:., '
...+: '~ . . Je.^.J. n1ost 'JSCJ ;n IhC stu,:,. .:i :JC.i
,
!,+v.1:% (Cit :ti:JuSc :t had het^ :hi :~tt.~i .S: S ~.^.:. .. .. . .~.,.
1%IttiC rn l;~t o( alt: `+JS!: work on :]ranoSencs:s !1J.: Ce" JJnO :. ^l::e . ...
n'tt SJ:tJniC :Jr ht 1Ut1;0i.:¢Isl Ki;U JCsIrCJ a ;11cIn1,Jl ur i1crnltJiugIC stuJlcS
\clther the r.tt nor the mousc. hoMeller. ;$ reJl!. wll]c:e ;r rr
-strJtwn of rclJtl~tl. weJk carcinogens or co.ar:ln.avis t,J!
_:it a:iilI:s to lecp out of the huTan enwusment ia:r . .-,
tn;:~Cl1.~ JI s-,tM1:111eJUs tumUrS :Cnddrs s13tlStl:a1
nlost dIt:l~utt. For eram,le. somc :.tnl;]! st:ldlts :!)t .. , ii:
t1tJt resrrplne may be a car;lnoeen or cocarc:nogrn
t.,l,,l:z the Jrjg iur hlch, blouJ ; ressure Jnd thereby Ir,:rtjsir.g
,;:tc!uj`tnC .Jnccr of the brclst tBostun Collaborlu+e Drua S.:'e..:.;-;: Pr,-
_ Jn:. 1~'sl Tlns t+bsluusl% cJlls for ]n:mal
cs jwd In sJ;h s;idles on cuntrJCC; u%e sterolls :.'t ^... ._.
s :~rn: Jrv ~u cs and ~J^;ers 1n :Jntr~.s R::s ::.1 _ -
tr;C vi r:r^;J'~ IitrJJJtnOm1S IHnT^u:.er e: :i . . : \I _. ' ..
t._.~ . I... r ._c1t .T.]v :+C tCS,c:1nt :J tnJ.T.ti:]". ....... _C",. . ' ...
... .. ' , tt". t,:.^.t +.:.I hJte s-.)nlJneous C71J^^'J .J'..i ~ _ . _..
.-
. -J a"t^ ,J \1C \%,::::_ ., t . es; . . ._.s ^e . . _..
T__:. 1'Jtr.s:vs t...te __+7-. :s
' . . .: .. . . ...,.e'1:c li r:
IS .1^.cw'1 t l! - ' .] I ]'._
Sone
S..SYp
T. . i: . . . ... ..;s .s . t t_ .. _ . 2! . . . _ - --
.._.~: .~.J~.itS ...J: .....'1 i.Jwc' IM ....:J:A
. - .. . .. ~,. , . 11.. 4:Cn.
.n . , . , .....t .`r^t1~JuntS. t9C 1. ^KnlI.n iS ^ajt .. . . ..
. .i.. .:~. j^J f ut:. u^:C .Ir'rriJl:. J: '^t'J:.:.ri^.[ S,. .-~ .. . . _
. i ~. .. . J .. .. . .:11 i eC-]f ,1! Jn CfL/.riC S)S;C'~ .n . '.. . ." . ' ..
CTR / 1 N -e..Jt ) 6 61..p "4.lt
0
Hcmrtrr C'u in f'ur:.r ' a:r, ;:,i,as 51
Ten¢beren, 19'I ~. Results are not reproductble In nuntnbred ,tnlmJls. li, lor
i.y reason, runr.r.^red anlrn3ls are preferred. hybr:Js irurn tu ur nt.,re Irncs
:a:t ee crollu:ed tr.at. as lona as the urt¢:n]I :IreS re:^J1n in :1MJVs
`_`e reYrodu:ed 'Of :epetlt:Or1 Jt etprrlrnents with ._ ..?7rJC:C pJp..Jtir rs
IP_e'. 'O..OI.
EPILOGI'E
T'.~.5 .C~iCa `]S t'.n ._ ..,.^.C~ ... _,es J' ^JI
.CS.']'.h. J s_.^tt.. .... ..._. ._ 'J.'I
L:. F::d_^]r. to ..!:.:ie .... 'o_rec
T'a _.. .'.;i'CS ."C .]':r .:C:J ~: ..__.Ci
...:~res . _ .. .. _ . n . Ci s _. . :r
', .'s J'. . ~., _sCJ
R:~..
_... .. . ._ ~, .]'n h.J",'Crs .. -.~ ., . JCs t\ in
. .. _ _. ._ ' ... _ __s _'.~ . .. . ... ~_','.'o .,J~ 's .:~... . ~r
_ . \.. .. ' ' . :~. ' ._ . .. . .. . . ._ e'__.i5 ~n ' .. C_.
is ?r. ..':C t :']~.. . ..`rC_ J'^S:e.' Cs
A
. . ~ " . _ . _ :... ... 'rSa. .J'. r ..'.CSIs r ,. . .
.. 1-- ]nJ s DCspr'C :S
i . . _. : i' .. . _ 'J ». J:r J_Cti rJle JJIJ ^Jx _r
_.~..ss.. . .. r!1e !1JGrslcr :n fQ.:. ;a:. Thc C-,an
... .. _ . 1 r; S :tajs '0 Oe rSej L1Jt JC t C
_.._ .'S .. :SC ' :S _,.JCt rCSuc[;G'
REFERENCES
a.:.-ns. R A icc9a. Recent experlments Mrt's s..n vvl:ng n Csr:Jn 1Jm
s'rs i _ _.... B.IL 5 :4-:6
i,:a^s R.A ;-- ;5 Fallthrckness horr.oQnfts of skrn +n RulJen nJrrsters
B..: 5 B. lAtStr 1
iJ]ms. R a. Pa:t. D I, and Lutz. B R. 1456 LonR tern rer.rsten,e ol skin
::
'.o^':c:j`:s c jnteveJ lamsters 4 1 -
a:'er, S I- ?K H:^]n ic;rosy ;n the Syrlan h.mstcr lrl 1 6461,
Sy5 r a^str I
I`+i'. T-ne l:'e`1avlcr of a Sudan strain ol /.r'rthmCn.,r Jii.,sCnr in
Pii:c!^co-+,ur _...:.r. a:ompanscn of s::uns of l fr..~,:n u fJm1 k
S.,: T ): ''i.J H. g 40 -01 -' I-
4::er. San1 Treo.lJr. 0: 4 ? I Imest:QaUons on kteJrterrineJn ki1JirJr II
tt:Sn:?!. .. ..P'7l fl SJl 'fl.!: IV~ Si).SryJ. l l'rl
At]'Jr:.. I 114 . FI.Cr:t 1r0:n S/rTJ.rS " . (I. ri+ _ fl 11'lt' l.
trJ^s.JlrJ `rorr :~e :r.~ nJl Nr!'rew i-v kt]rs:'.a I IJc%r I- '. r, ~r
:' ._ F
I:'*r
CTR HN 042~'.~ 6 1
a 1
S2 F
Altschul. R -a6 Ft,^enr,enta, :ho;esttr.l ar:er:.)sc.e:.s.s (-`a-::s
in sKeic:ai mus:.r .a4 -r P:. '! - -- __:a
amol,l. F 4 Jr 1as: Tne ;reJuct.c,t .:ar:cus .c,.--.c .. ,: ....
. - ,
of namstrrs ic:cr::s _a-a::.stv l';,`..c rl,_ : . R;~,
AshCel. R I,1s'. The me:at Jiism of rat :r; romas enJ oi :Jt -a._
E
i:cs R 5?c Tr 1fiJ f!.r 40 Sc"-a5
Ba;usz. F. IQ6y \1}ocar.aal iesrons A rca;sess:-:cnt >i ;~r
;ai:(um :~;lamate \ rapr 2231c. u.4 t a06-30'. -
Balusz, F... Baker I R.Nrcon. C. W and Ftc^rbur¢er..F IjAo
hered(tary my. ocardtal Jegeneranon and congest:%e :urt :i:.-;: .+ a
st:jrn of S~ r.jn hamsters. :i nn \/a,:J Scs. 156
BaifourJones. S. F. B. 1939. The expcnmentsl :r3:+s:nrss:cn oi :J;
the goiden hamster (C'iccr,u cu:rust Inr J l rr-, ---~3
Bernfe:J P. anJ Homourger. F. Ia"_ High n:;etme to;e:.-;r : i,::arn
guiden. hamsters Tnr:co! Aprl. i::1: r}:a
:. ..-.r, -
Bernfeld. P HomDurgcr, F. anJ RussfrelJ. :1. B. I+"s S::3:-!
t!re resronse of rnbreJ S>njn ha:nsters to c:garccte
\:r/ C:ncr Ins,. S 3(3I I Is 1-I 15%.
:ra-. ... .:~
BiIirnF.J:am, R F. and lii:Jemann. W 11 1058. Stul.es of
;mmunitv. .aw % )' S. "3 0-0-056
R Eja_1 Sd%ers. w K(eJ t,)c I. .. .~>... ;r.
Inst:tu:e Pr:ss
B::Itntt.`am, R. F. SpMchu.k. C, H 3r.: S.:.rrs. w K I~oJ __. -<. -..
a:o.~^ra:~`:.:5 :r:;es of the S>r,vr ia:nste: . _. .._ _
J H.rst,)n E J IJ:a T-t
.t i .. ..i: - . :'J .., 1v1SterS r?i:Jw,^~ a' .' ..i. ...... .:1 . .. .
. :0 10
B-a_n II (, I.. L`er d3s \,:r._ ..
Hi-s:,: r a . r:; : 7<. ~ : ..
6ra.r \t i ia H.`vr.j: - 1!rJ .: . ... :fr .. ..:s . . ,
a. / /'- . . . . ,
~ -," \t 1 . i^ ProJ,.,..:n i-,. .,:e ;r3- _.
6:.,, Le c'.rr \t . \te:ej : a ~ _ - - ~
. .._ . :i... i~. :~ . .... ..!'.c(_, ._ .. _.-..... . . '- - -
L: +.s . . ^.~....s P. S _ -
B:cu,. G 0 , \tue:'.rr R 0. \te:.ra R
'ir.s-'.ss.o- :i S: L~.a e-. ,-.;....s :~ ... -._
u : -n03
C`;j:lic,d. P 0 .-.j L.-.j- C P .;!a 5~~._ ..::. ..r: ... .... , - .
Ceen. K A . Po-e.,. C F jn~ \tj:.. H , ~a5 T-.. ..._-.se . ' . ..
Chute. R S. ^:ners. S C anJ w a: . , S .I..... .,:-.r; j ~ _
human :jn:er 11. Hv^.lster Lheek po.;:n CJrce
Causen. t) E anJ Ciark w C 1043 \'.:a:njn C re;,,.,:erne-,:s ::- ", .ae.
.`.3:nster ::ur I .Jon, 15: 300-301
CoDurn R 1900 Study of tooth storage J. Denr nrs 39 'G"
cr, m I _ I I ! I 042iurP \sA 2
lfamsrr C'tr ,n Furuc Tnccrol.qv 53
I
!
Cohen. S N. 1961. Compartson of autologous. ho^ro:oaous. and.heterologous
norTal skin graits in thc hamster ;heek ; ,;u.!t. Pnc .S-ic
Vr. 106 6-'-0S0.
Co.^ley. A L. lui6 Frnto:izar,cn of pl]tetet Jgglu::nJnen thrombt :n t!te
!:3:^s:er's ,o:..n u.c `> `:r; ar,n I eJ P,c '.I- :--__ t>`str. t
C=r;er. H 1]nJ C.)`.^ `\t. L i,.u T~c h,o;og . J:J¢no,s ot !J"ercu!osa
tCs:s ~^ t.^.e 5~..-l ']^'ster J^j .^e
Cra^ F B 1
t1._ I o-,
`e:,:on `. ,, c.t.on
C...:{r. l. . .~.. j..+'.. K L ..°1
^r5i s.'.j
De L,-]:... 1~. '! ..... ~.n. 1 B.^!1 J^ H.
. ~3+ A'. ..~! _S ~] -... ., . .. .*c."]':S1
.; :~= J; _ -. . _. ..~ . . . ....., t . : r . ~~. . I-..
: e... r . _ _.. ... :n
-.]r'...a ~ .-. _... ._ ' _ .. . . :. ... . . .. ~-. -C t. :. .:cr
l1rr. a ~ 'A ~ ~. ]° D F 1 :Ja
. t; ... ....,_ ._-. . .... . . .. ~; ~^ ]^i:.. . . .. .. _ .:, 1-
l.
. - . ~ c_., . . I - ..... Lc s-_ra PJ " .
~. :C'.... N ~ . - . .,.. r^._, ... ... _ ,..~i .,. :-c c:c,t ., .c] .:t{
II P L:' {-,. \' , Ke:^.2cn. G saJ
cn ...
`.]-:S:.s
a:err]: es:r~¢en
..:oc _. .~. .
D ^^. Tr<3 ~ : ^. :gy o: ^~mmJry wmors .~ +n,.e In r'e ; h.s,~
_. . .,, . :d cJ , eJ. F Hnmt.+rger. ; p !5->ii ew Y,]rk.
Hil..cc
Ea:_^.. " D, \]- Hc-::k, u]^d kietkte;ohn, G 1445 St_::es on :.:e
{t:::c¢- cf ;r;,-tary atyp,cal pneu^ton:a III S:eu:(:c neutnl zatien of
.,~e - _s -. .._r.]n serum l F.ro tG-J S: 3.9-3J_
E^cr.._. U.'t.>j,{. \tW anJ SJto. K 1968 t Jr..aatcn:,:y n the ^amster
]Cm,nts:creJ :]CetjmtJoe'.,,jre:+e ]n,1 3methylclol-
J8!`rC'C 1-1-IiC
F:rr:c. L. \I ir .`1 S]cj \luseaNe. E. R. Io'0j Colorado t,ck !e.er
isej:ion :f :-e :n:s :rom De-..7tentap :~Jerson, in n]:ure and a
I3tcr]:c:y st ~. .'.e .r]nS'rt,Siton uf thc wus :n the ...k 1 lm
mun,-i o+
F:cr:o. L. %t S anJ k1,]serae. E R Ia' n D CJtor3 _c r'e~er
Isc:]t:on uf the ~tr:,s ;r,,m .:^+ Lcng
Ii:anJ. New YJfK, + ith :m:nun,-Aog::]! :::~pansons bct-cen eJstc:n. and
-euc^t i:ratns l (N4
Fo;.;s. R H. 1r i., ter ,n :`e "]^s:cr Per S.)c
Ez: b . sfr_ ;r0 :03-:lj
crR. IIN 042266=.~
A t
r. Nom~r~r
S4
Foil;s. R. H 1r 1Q5ob. Thyro,d,r,s res::iunP fr,;m
rcJrae ;) hamsters wsth h»erplastt; goiters. P;c S.c c s: 5. _
.
102 i:5-s.Q
Follts R. H., 1r. IaSQ:. Studies on the pathogenesis of U,:er T:-s
4ssoc 1m. Phrsrcons ': :65-:"a.
Friedman. L.. Rt:harJson, L. L., Rrcnar.4son. N1. E. Let.`c,. E 1
W. C. anJ Sauro, F. M. 19'.. Toxic responses of rats :o ::.]m];es a
chow and semtsynthenc dsets !Nar: Cancr ~.nsr 44 '. -"o4
Fulton. G P 1Q68. The golden hamster in bromedtcal reseau:h In r-< <-.
}.7nNi /Tr !lolCri ]nd usr :n .ni.:rc.! .eicach ed. R k Hiftt]1.
P. F. Robsnson. and H. %tatalhaes. cD 3-14. Amcs. to~a S:a:t
Press.
Fuiton, G. P. a:td Lutz, B R. !95'. The use of the hams:er .htt:
ctnephotomurosraphy for resear;h os. the
trowth, .nd for teaching Durroses. B+n tlee r1 3 1:-iQ.
Futton, G P., Jatkson, R. G. and Lutz. B. R. Is46a The ust if
Pou;h of the hamster. Cr+ccrus Jwarus, for small Ilood +essels rmotton ptcture r. .Inas Rtc a6 S5a-:
Futton. G P. Jacl:son. R. G. and Lutt, B. R. 1as6t: Ctnt;hctc- :- _
ncrma: +'tood crtca!atton in the cheeK pouch vt :rte nars:e. _.- r:. s
Jupstus rmotton ;.;cturel .anot Rec. 56.53- r3Lrs:r r
F:I;on. G P.. Ales. R P an: Lutz. B R 1953 *n:e
]nd %asculas fr3tilrty in the hamster check ;ou;h a:ter :. ..::i!_.;n:s
0 '. 40-15 :
F,,tton. J. D IQs1 The therapeu;:c ,f scTt re~er ._:_-:_. ..
:n Lr.s-TJn a +nfe;troas of go..:en hams:ea
sr .a.rn T,,: uc. ly--i1:
F 1,r-J IGman. O)~01 ~aran:gtres.s :n ,.,. t.;.,-...- ....
of :`e Syr,an ha^ate: (Cr:.e:L,s
G.,... aa. !- ]r.J Pei1]+c. 0 l , -)Ja T`e hrw. :s ]n ~-.. -
?r .'t stj+'r% of 1 n Nr:. ; : ~ ; .\'...
t/:JJW:1 L G '.e34] Dede:.^.a :n n]-sters aife:ted w:c-. . ~ . . _ .._
I _ ^ .:0 3 6
L G toa5t: T-.e of
rOt ,.,. ]Ca%tt) of
r:JOJ~. L G.-: %l]rs'a,'.. F B.-a5 T'sc ^.a:-~:: .... ..:_....
1
,rar ]:, xi .Q-: Hj-^stc: .':ee. _:n ;t_
cor- ,; ].^.1 'e0:,as:c it,.dtts 1' , -. '<
.a _ .
F H:m: :grr %c . 16 ; p 3ase, 5
rr,..tt!s, a Sr ..31 f.rt! er rii;errrerts ~.. 'e
+ah tut7et.,e '`a:.,a and ;:1e ~..,e s::L.'. _. +..- .... '+.
~Ke.st ! rl.~ LonJ.)n 41 :^D-:65
flsnzl:,. > H I9oe 7rar<^!an;at::n-G:a`:tr~ 1- ~. . -
- .,. r~ .,i ..sc ., .:c*_. ., t s.lci~ e.: R
anJ H. % 1]ealhacs, :P 'i1-:51 4mes loa S:]:e
IIrnJirr, \ H l9-:. Studies of ;ardsa: alloetaits n S):an -]- -
I'j: r.;. ar vrc S~ P:n h.-^ster. e1 F.
S-Q Basct S K3raer
Handttr. A It and Cos^+an. E 8 la-3 A stmpL:ie.1 ],%,:
tktn gra;ts:+8 Lr;e S<< 13 1:93-1:45
CTR MN 042664
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i
J scsse . ., c.s .n S.r ]^ ^]-r s:ers In ":. .; r ,.e
_ F !! _ .cr. . ^~. . ~lssc: 5 I:ir .
1 R
~].`..
S
F ].^.j !rS:e' . S. S C]r::^JQC.^es:S St.J:es ,i .r~e~. jn
~-s e s 6 c]s! :1 :cr .. ~u:uJn tY r~:^Y..~~:]-t renc '.e :^¢ ,' ~.
a:.. . - . v'.' aj
F I-: K_,s`.e!d, A B 19'0 1n :nhreJ !,ne .,f SY~tan ^,r.,;ers
.`re;uent s;ontaneous adrenal tumors. C'a,trr Rrr )0 tnv-?ui
Hcrr.~ r:::, F BAer. 1. R, Stton, C. 'A and skh,tncr. k:'e: I'- nsrY
fcr.c ~:.zeJ ; :IyTyopathy ind ,3rJ,j: necr:.,s n ,rn :~,rc: r.c ,.f
S.:.a:s -.^sters. t1r4 Ecp. Barclr 0 339-?ac
H:^,b_rger. F.. Craube, S., Fppenberger, M , BottJonoff. P D and ,t:n
C'~ : Y55 Sus:e;ttbtltty of ;erta,n tnbreJ strr.ns :f ha:r,;c:s :u tc:s:u
jer.:: e::s of thaltdomtde. Tox,i.uf .ippl !'ru-+dL ,i ':5 t oeo-o- F. Ffs:e':. S. -S., Kcrr. (:
S3nd Russt,clJ. X B I r'_ 1,v1.ntcJ
af m"reJ str3,ns Jf S)rl]n hamsters ta ..nJu:!:on ot cut
:uta-eous sarcom]s and mammary and gastro,ntest,n], ,~r.,norr,s hv
]'1J I]strtc wmtntslrattJn u( ;J~Ynu.lc~r !I.JrJ:~r!'Jns
Krs 3: :50-366.
Ho^;".rse:. F . Hjr-4:er a and BernfelJ. P. ly'`1 Hometrinsrlincit:on of
:i:%nRes of ;;g;ret.e«poseJ S) nan h3mslers Y
t!.-1 la9 1a1:-1315
Hem!ureer, F . Han.1lcr, a. and La:rJ. C IQ-5C. l n!Gue propert-es of :n:ireJ
+ S~ r:]n !~a:.^.str:s ;or zar.rn,;eenes:s stu,;.es h . S,
~ Horr,hurger, F Rjss:c!-1, a B, Ne:sburger, J. H L.m. S.(~ . S H.inJ
µc,s:urger. F K 19", .5g:^g ,`..nges in CDI = IluM It ,t ... c rcicJ
, un-4er s:3ndir~, ;i^orjtory canJ,t,uns I%ir, ;, t: "t 1' ?--4c
1loTsrrt Lse in Fur:rte TJC,~u'.. cs SS
Handler, A. H. and Cosman, E. B. 1974. SSkin j:!ogra(t cit'6-hanges among
tnbred stra:ns of hamsters. Lr!i Sc:. 14
1~55-1ao:
Har..!er, > H a^d L]:rd, C. u la'S. E!e:!rJ,arJwgr];h:; r;;orJt^gs for
assess:^g sur"~]! of card:]c al!cgnfts :n thc n,:^;st:r ,1ccr. ; u:,h
S~ tr:+ B:"'. s.'.'_ 1s5ta1 il::-11a0
H. ]aJ 1e:w.ua, G IQ ca T~e ::a^s^iar.tvtcn ;' '+urrsn !era
.3 sn :'1! tasues in m::'»!s %,..c' (.~
a!::i C:',t ~'crt I 1`
Har:s. PN ..ar,Jerso^. R C:rJ Cl%er, K. K luao The a;:.on o: j:locan.
see;.,..... ...:our3,,. :n ..e 1j-.,tc: J
-cr.. C H. -aJ H3-:rurec. F -.. Sc~ :es !,.e aE:nz
Have::]r.y. L H 1
oC S% .^.J.1 ¢=.,~,en `:]TSt:ri F'-c.t . j:c . . I^. =1 8j:,. S I:]-e_e
.,J . . \ _- .,sncross ]i ..^.e . es: -e ,-_.,-. n e...j n
]"n S rs -t-
H.r7i.:. S . . 1..... _1:..._ . ..,. _. . _ ..~.. . .,...:i:,.. c~ J~ S. .~:1
H.:s; . R
'.
H: In
. _ . .... c~ F !1. .-_ ' - .
I
L. r f R 1{ f"'f 042665
A 1
50 r ll .:-,;;.
Houch:n. 0 1 3a:. \:tjntn F InJ nus.Ie .:eg:ne-3:.: . .n .ne
l'~c LIIIr II--I18 1>hsrr 1
House. ( L. Burt?n. C.( oo:er !1 sr. ; i~Cers;a. E'. aia
i.e ~..
tion ~( neon;ItJl ;an:re3s n the :heeK r.,1rm3; JrJ
hamsters I nar Rec. 110 3 16
H:-use. F. L . B:jrton. C . Coe5,^er. H. Jn;: An.lers~n. E io>~` T^.:
!ton of neonalJl pancreas snto the hcek , ouin of :nt J.:ue,lr. :.J''e:..
h3mctcr. h.rJrt'rinn/urt a3 ?A9-301
Flutpcr. W C Ioa:. Occupational tumors and allted Jtscases S;r:r;;t..:. !.:
Charles C Thomas
Ilac, tr. W C. u;Ic> . F I! . µolfe. iI. n. R.lnu: V F.
BIooJ. F. R. IQ3R. h.itten-sentil proJu;tton :f r,jJ.:er s
hv jiJmintstrat:on of .9nathth.lamrne J l-J il.: T r. : ~^--
Humes i. G ,rnJ \.:rs. R P \ie,ular ,1)jrges n the .nce. : +
the gnfJCn hamster Jur1nE infection rrth Trcn:r:r:a a-:r
R.c 114 103-113.
Hurst. V.. Mullrt. P . Frr.r,e. II F . \u:kolls. J and %1Jrs~J
^recress rerc+rt in the tJCtenolagtc lcpc.t ot t`e :Jrits
crarn. (.rilcFe of Dentistry. L niere,:y of CJ::ior^:j. J' :1. -:
:x 430-a3:
J II Iui1 I\; crrnental r,ckets in ene hJmt!cr J'. . ---
A.rsf:+:Jn. D (: V \1 J1J IlJrnc. ( ( :Q-a S;,,,;.es ... .. . - E:
°!nJing n , in tsoiiteJ h3mster triche3s Ir. i cr '. . ..
. rr~ t:r :r~srs ^J ::swi r, eJ. E. A,r.^e an.: : r?;:.. -.
~a-c'a \eM ~ rA S^r.nger\ er.ag
Ai,sr.. C I )?9 I-cianges re1.1ra!o1res Jes
.:%,nJ+gcs in arouseP ub4rnatorsl IMa P- s.;. Pr.: .
IS IJn "-I:I1)
Acw. P 11 Ii-o f)ental :vtcs I .nt S> -Jn ^a-.~
,JrCS J.lii1y ;n J'.mlls iej Js" _..lS I nrr Rir c ac-101
A:.rs. P II J-J f)re. P P Ia4aa Dent;ton of !rle S>r:a-
A.yec. f 11 JrJ f1J.e. 1' P
.nt .:pn af ,^.t S~rtan `.3:-s;er I l)r-r Rcs
tJA : \ ^rc:.m,nar,. in
%^ls:ers ~: . '!,: B.. :0
!t i,,nerc!]:ed .n S - -.J- c[e. - -
~ ~,.:. -1^trer. e. F Hc^.^,.rger ~_t .o. .. - ~_...
~ A~rtrr
A.r.^nin I/ JnJ \ t~rJ. F T 3^A -i.-:J%!-1s In r -: t $. z -lr"
^.s . _ _ . .. .
. ra:h rJ R 4 lloffTan. I' II Rc";ns: .a-z Ht.5.r.a es ..
.. :~J \ me% 1~.J Cta:e l n;% e- , P!:ss
A,%N . I t I Thc .rrrte.7 ate and rroi+eeJ et'e:: ., -ce _:se _-
n the !eslts JnJ germtnai eritnei,um oi r.e :_ :e-. '_^s er ... ..
. .rirnll ! tl.rrr.~l Fg i`t-cJl
AonJ% Jhi. \ II :: -nJnn. U ind w% nJer. F L 1 4 -~ \ s:
.Jr,mu~enrus \II fplthelul chanRet trddu;cJ n .^e r;'e!
trJ.l% ~1 ~~ri]n Co1Jen hamslers O,v cijlre::e s:'.,~r.eJ ..
/rir ~ ;r11 1-5 -1089.
Kul:.r. P l It1A The genett,3I JnJ ^ie%.h3nicil r^^.rl:es
,hromosomes IV Tne tolden hamster J(:entr- 36
....."rI _ l II I 042- 666
Namsrrr C'sa in Future Tu.crc.lnw 57
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Koller. P. C. 1046. Control of nucleic acsd chirge on the Xchronsosome of
the h]^sster. Pr,,, R S,). B, ! I?3 3l 3-310
~ Kopro..skr. H]nd Co+c H R lyad,. StuJ:rs in .`Il.k emhryo ]da;+tcd r]bses
.:res I Cua~.re ;h]r]:tcnstics ].^.J , athoacn;:lty J h-mun! 00 : 33-
Kr]snc:.~R I and 1'.un¢, G I,;5B. Ro!e :i r.".,.ro^:_1]se ]r+J :he hy]luronl:
a.ld ,]; s,.!c in the sur.lvai and J:estTlcatwn of group \ strr+to:u:cs in
The ':,Tliitr j^.J` a'1u re
$
Lrrsh. J F . Jr . a^ :n »hlte mlte ]nd
i-
L]rsor C L I3 T`e i':`t vs;an 'ssT+s'er ICr,errus
Le^IC.. 11 til L. , B R. P-. R. L.!1j-a'cr. 1 FI ]nd Patt. D
S_. :]. Z-. t .. . :~ ,n-c ,rJns.-:J"1aJ :o hJmster
.. .'./. ~.1,... ~ t .. . . . -~r .
f) seiscs ~; , .....s , ., .. . ..~ u aT r~r:,:J
.-
L.... g R F..._ ~ P P;c 17) I__ l!,.^.,'cr >!I :n50 T1c vovth
. _ : :n .-.e ...:. . _.. _. *1e -.a:T7steC ,tl,sp.
L .. o : F _ . _ , f' ~c.. \.:r, et P
e s-... :c ....n Jt.., .__rn3. i^J a:.F-j^, -eo-
..
\1 + T`.e ."e:t of 'W~erna:,on on the
~ ; ... .. s]:.v^;] .n t`e !;]'^s:er (. .-t rt, t 14 -5--8
r;-' u T,94a Dctt:, .ri:.:n j-J rrjc^.e]t:on n s~,eletal
.:Iy .'1aTlsltfs Js a '']s,s IJt' ^iJJ>>,Jy of
~~.~4 v:.'ltf Jntl.'ys:ru;.'%iC ivCStanCeS ~4 d! Rtc
\1;C ».`'A F 1The eife:ts of ar,hlCecwm) in tne gulden hsmsier,
P': D th:s:s L nsvers:ty Southern Illinois. CarnunJale.
`1 C 1 44 Sus.eptsbllst) oi the tro:.'tn h]mster t/rtourrcerus
_... :o ^']j-je P;jD::c Nej!rh Rep i`+ :34-:?6
\letcrs. '1 µ IY50. Studies on the adren]Is o` thc gulJen hamster t('r,irrus
1.:r:.s 1 in rel]tton to ]gesng. anar Rec 100) t\rstr I
'' u anJ Chanpper. H A. 1956. A lssto(oglval anJ c)tolog cal study
of :.tie adrer,a: R:]nd of the golden hamster t( I,, fYJ db?JfYJ 1 in relanon
to age. .4nJr Rrr- 124 1-25
\1_':s, D II Ia'4 Prcnat]1 DES and vaginal C] :n offspring, J Am. t/rJ.
4 :!cc ::, 4 7 1 - 4 7 :
\!Itchct,, D F. 1046 PerlJont]l disease in the Syrian hamster 1Am Drnr.
.I ssoc 19 1 "-18 3.
M:tchell, D. F]n.4 Johnson, W J 195" Fffe:t of :acetyl]mino-l 3.
~thsaCt]zole:sulfor.m~~e t Dlarnox 1 on -c1til ;anes rcw0an,e In ham
sters J Dent Rrs 36 3-:-3',
Norr;s. A L. IQb1 Fa.tors Influcncmg ecpersTent]l ;]resncgenests in the
n]-nster check ; ou:h J ncIr Res 40 3-1 5
\loses. N1 J,,nC lerg]nsan, G. IJ4: Deso%):entose nuc:clc ]tsd tD"jkl
:or.:ent inJ ,)totaxanomy oi several (..:ndr th.mstersl Grnercts
3- 00'-608 t A^str I
{..r f f'c. f f N 0422667
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Muhlbozx. ' 1 ]nJ ~on F"en`t^rst Tc-g:eqe^ 'A P J R :';
,f :'J;J::tr:stics in.:nf'red ctratnc ,f '1,.t ,
^;, .:0-:30 washtngton. D C
\1\ers. II + I ]r.J F:anagan V D iJ>5 Pre;c:n,r.]r. , _]
tr]ns;:Jn:3non te:hnres in tht hamster. ! Drnt K,s ?s '.
\tyers. II. I and Flanagan, \'. D 1458a Studies t^~oi%t-j
effe:ts on results of replantatron of hamster teeth..an:: ~Re: ;:0:3:-
s33. t 4bstr l
\tyers. H. I. and Flanagan, V. D. 195ib. A.ompartson af rrs-:s
from transplantation anJ rePlantatton ex;eriments us;nt Syr:]n -a.-:5:e.-
teeth. a rat Rtc 130 s97-c 13
Orsini. N1 w. and Pansky, B IQS. The n]tural reststance :. :-.e
hamster to coichtctne. Sr..nct 115 b&-5a.
Ortiz F. locc. The relation of aJ~anctng age to react;%ity of :r:e
system in the female hamster. .tr:or Rec 1:= : 1--`?- ,
Patterson_ W. B.. Chute. R. N and Sommers, S C. 195a. Trs-S;
human tumors into corttsone-treated hamsters Conctr R: t,
Plotz, H.. ReFan R. and Hamilton. H. L. Io4: Tr»sm:ss:on of :-- .-.e
.
strain of poliom)elius to the Syrran hamster Prvc So: tr: i
51
Poel, W. F. Iooa BWJssaVs Aith rntreJ mt:e T-.e:r
~i. rtJ jrirnal. In 1'r ertf rq cc^raat ::J! :.^r. .. . .._ r
llon:rJFer. %ol. 1 I. rp 333-1oO BaSel S
Poor. I. ;j°' Bre;he;lJst,e homotra::s;tantation of `3rs:e: -.._.. a;.
I.rr:'Jry rer ort. T~1 ~JC.~ :r Ru: 4 143-144
i _,: r I' l'Z: 4
t:er B:.`, l1cJ 0'
Pr ce J\1 ! Oscr. B L . Steinfe'J. J]nd L:y. N L I ;'0 9]::c '_--rs .-
rJts rJ ':.3ne..:amsne and `;gh Joses of a .,:'Lture _. :y.._-]:e . .
rJ_.`.Jrln ~. lrtr 16- 1131-11:.. -
Rt]J. C I' I-1` 1 II. ~ t~ ~.iD s *^~t. ;n :ne SYr:3n `J-ste: ., :
Kc]g,1.'R l. L,'!rt \t G Il,;user J E__ A L
sIa-s:0
Re]gan. R L Lrii ie. \1 (. II]::scr J F ]r a Br_'. -r > ~ --
l':r-J-.;.:c.:al )t'.dies cf ~t~\]s;.t rs r~'. ] . .- ~ .
N
R:]tt~r R L. L,:e. '.1 C. H]:cer. 1 i a-J B:_-, .
:: ...S _.
t/c o^ :a= -al
R L L.:,,e. \1 C. L J _ 5... ~ --
\to
R:agan K L. Ste-]rt. \1 T]nJ B:.ier-,ner, a l .. i:._ --
ra*:.s Strcet %rr;ts stra.ns in ,^e S>r:]" r.,-s:e -
tl,-J v 1 'y i.-C~
Rt..e t I445a Homot=;]su,: tooth -]- s-
.).1. Saq 1- ?6- >>
Kesni.~. B. Fairter, E\1. jnJ Fu.tun G P. 4-1
:nnsClanteJ into the :heek pouch of t':e g.:,Jen r.]-rs;r . _
1, rr r(%i:, jtlt 81 39s-}vo.
Kr.harJsc,n, F L. I't:' Inc,dente of r:+arnmJry
h.t+riJ micc treated %ilh stJFestrot for %ar~inQ ;er.c.s . -
lnir I!s 313-e30
c-rR MN 042668
Hamrter C're in Future Tjcrcolosr S9
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Robinson, R. a 96:a. Anophthalmic R'hites- A mutant wlth unusual morpho-
logtcal and pigmentary properties in the Syrr;in hamster. am Aat
96.183-185
Robinson, R. I96_b. Genettc studies of the Syrian hamster. IV. Brown
p:gmenta::on. C:e^rr:c: :? 51-8"
Robrnson, R. lQti_c Genetlc s:,:J.cs of the Synan hamster, V t;'!:Ite bmd
Heejrrv 1 " -4b6.
Robinson. R. ! QoB. Genetlcs and kar~ ology In T-:r S.,,Jea ^amrrer. Irr
`:~:cqv :nd ,.Je -7 m~~.;o! tJrdC^. CJ R A H~fFT~n. P F Rotason,
jr.J HM3gaihacs. pp il--: Ames Iowj S:;:e l noerslty Press.
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~ ~~ ~~~ 04'2e-(&*>~~O
