Council for Tobacco Research
Chemical Carcinogenesis in Syrian Hamsters: A Review (Through 1976) Progress in Experimental Tumor Research, Vol. 23 [St Hamsters Are Useful Experimental Animals for A Variety of Carcinogenesis Studies]
Fields
- Master ID
- Ctrmn00041967-2810
Related Documents:- CTRMN041967-2114 Deposition of Freddy Homburger, M.D. [Deposition of Homburger in the Matter of Broin]
- CTRMN042115-2200 Deposition of Freddy Homburger, M.D. [Deposition of Homburger in the Matter of Broin]
- CTRMN042201-2213 Chronology of Events [Letters and Chronology Outline Dispute Over Publishing Research on Cigarette Smoke and Hamsters]
- CTRMN042214-2228 Inhalation Carcinogenesis Experimental Investigations on the Effect of Cigarette Smoke Inhalation on Small Laboratory Animals [St Effects of Long-Term Exposure to Tobacco Smoke on Small Animals]
- CTRMN042229-2248 [Cigarette Smoke Inhalation Studies in Inbred Syrian Hamsters]
- CTRMN042249-2251 [Comments and Suggestions on Study Titled Cigarette Smoke Inhalation Studies in Inbred Syrian Hamsters]
- CTRMN042252-2269 Strain Differences in the Response of Inbred Syrian Hamsters to Cigarette Smoke Inhalation Journal of the National Cancer Institute, Vol. 53 [St Cigarette Smoke Caused More Cancer in One Strain of Hamsters Than Another]
- CTRMN042270-2294 Progress Report for the Current Contract Period and Renewal Application (with Budget) of the Project Entitled the Determination of the Usefulness of the Golden Syrian Hamster As Model Animal for Inhalation Studies [Cigarette Smoke Inhalation Caused Macrophages in Some Hamsters' Lungs and Reduced Weight Gain But Did Not Affect Mortality]
- CTRMN042295-2298 [Summary of Meeting on Status of Research]
- CTRMN042299-2304 [Draft of Contract for Inhalation Studies in Syrian Hamsters]
- CTRMN042305-2308 [Comments From Counsel About Contract Form]
- CTRMN042309-2316 [Agreements Between Ctr and Bioresearch Institute and Bioresearch Consultants]
- CTRMN042317-2345 Skin Painting Studies in Syrian Hamsters Skin Painting Techniques and in Vivo Carcinogenesis Bioassays Progress in Experimental Tumor Research, Vol. 26 [St Skin Painting Caused Tumors in Hamsters More Frequently Than in Mice]
- CTRMN042346-2350 Pulmonary Eistopathology of Hamsters Exposed to Smoke [Histopathological Findings of Study of Hamsters Exposed to Cigarette Smoke]
- CTRMN042351-2403 [Expanded Study of Mouse Skin Exposure to Whole Fresh Smoke Condensate Compared to Skin Painting Final Report]
- CTRMN042404-2405 [Ctr Delaying Approval for Continuation of Smoke Inhalation Studies Seeks Guidance in Procuring Funding]
- CTRMN042406-2406 Bio Research Consultants, Inc. Consultants to the Tobacco Industry Since 1959, Is Now Offering A New Technology-- A Fresh Smoke Inhalation Method [Offering Smoke Inhalation Studies to Tobacco Industry]
- CTRMN042407-2422 [Results and Methods of Bioresearch Consultants' Studies Are Property of Ctr Inhalation Studies with Cigarette Smoke]
- CTRMN042423-2423 [Disputes Claim That His Actions Are Breach of Contract]
- CTRMN042424-2424 [Suggests Meeting with Hockett and Jacob Before Presenting Paper]
- CTRMN042425-2425 [Summarizes Conversation Publish Scientific Data But Clarify Source of Interpretations and Ownership of Patents]
- CTRMN042426-2426 [Abandon Bulletin on Inhalation Studies with Cigarette Smoke Delay Involving American Society for Testing Materials One Year]
- CTRMN042427-2427 [Abandon Bulletin on Inhalation Studies with Cigarette Smoke Delay Involving American Society for Testing Materials One Year]
- CTRMN042428-2473 [Manuscript on Strain Differences in the Response of Inbred Syrian Hamsters to Cigarette Smoke Inhalation Submitted for Approval to Publish]
- CTRMN042474-2552 "Final Report on Contract C-191 A Project Entitled "the Determination of the Usefulness of the Syrian Golden Hamster As Model Animal for Inhalation Studies"" [75 Weeks' Exposure to Cigarette Smoke Produced Various Results in Hamsters, Including Macrophages in the Lungs, Increased Heart and Lung Weights, and Decrease in Body Weight]
- CTRMN042553-2553 [Encloses Assignment for Patent No. 3528435 Seeks Direction in Withdrawing Paper at Federation Meeting]
- CTRMN042554-2554 Sugar in Tobacco [Deplores Speculation in Tobacco Controversy Reports on Successful Studies of Smoke Inhalation with Hamsters]
- CTRMN042555A-2555 Fluoride Ion Excretion After Inhalation of Several Fluoroethylene Derivatives [St Exposing Rats to Atmospheres of Fluorinated Ethylene Compounds Increased Urinary Excretion of Fluoride Ions]
- CTRMN042555B-2555 Pulmonary Histopathology of Hamsters Exposed to Smoke [St Exposing Hamsters to Cigarette Smoke Resulted in Effects on Pulmonary System]
- CTRMN042555C-2555 Response of Rats to Pyrolysis Products of Fluorinated Polymers [St Physiological Responses of Rats to Pyrolysis Products Included Diuresis]
- CTRMN042556A-2556 Tumor-Associated Alkyldialacylglycerols (Adag) and Other Lipids in the Thymus During Irradiation-Induced Leukemogenesis Pathology 2202 [St Analysis of Tumor-Associated and Other Lipids in Mice Following Radiation Doses]
- CTRMN042556B-2556 the Endocrine Role of Dietary Lipids in Mammary Tumor Formation Pathology 2203 [St Mice Fed Lipids to Determine Effect on Tumor Development]
- CTRMN042556C-2556 Effects of Altered Dietary Fat Intake on Serum Prolactin Titer Pathology 2204 [St High Fat Diet in Rats Resulted in Increased Serum Prolactin Levels]
- CTRMN042556D-2556 Altered Incorporation of 3h-Thymidine in Hamster Tracheal Epithelium Caused by Respiratory Carcinogens Pathology 2205 [St Hamster Research Suggests That Dna Damaged by Respiratory Carcinogens in Vitro Can Be Repaired]
- CTRMN042556E-2556 Histopathology of Respiratory System of Bio 15.16 Hamsters Chronically Exposed to Cigarette Smoke [St Hamsters Exposed to Smoke Had More Pathological Lesions in Their Larynxes]
- CTRMN042556F-2556 Peritoneal Mesothelioma Pathology 2207 [St Study of Patients with Symptoms of Peritoneal Mesothelioma]
- CTRMN042557-2573 Strain Differences in the Response of Inbred Syrian Hamsters to Cigarette Smoke Inhalation Journal of the National Cancer Institute, Vol. 53, No. 4 [St Smoke Exposure Resulted in Reduced Body Weight, Enlarged Heart and Lungs, Hyperplastic or Neoplastic Changes in the Larynx, and Microinvasive Cancer in Hamsters]
- CTRMN042574-2591 Experimental Lung Cancer Carcinogenesis and Bioassays Cigarette Smoke Inhalation Studies in Inbred Syrian Hamsters [St Smoke Inhalation Produced Hyperplastic Changes in Hamster Larynxes and Decreased Body Weight, But Did Not Affect Mortality Strain Differences Were Pronounced]
- CTRMN042592-2599 ""Smokers' Larynx" and Carcinoma of the Larynx in Syrian Hamsters Exposed to Cigarette Smoke" [St Smoke Exposure Resulted in Cancer of the Larynx and Severe Epithelial Changes in Hamsters]
- CTRMN042600-2603 Homotransplantation of Larynxes of Cigarette Smoke-Exposed Syrian Hamsters (38760) Proceedings of the Society for Experimental Biology and Medicine, Vol. 149 [St Sections of Hamster Larynxes Were Transplanted Into Cheek Pouches of Other Hamsters Hyperplasia Caused by Cigarette Smoke Persisted Up to One Year Without Further Exposure to Smoke]
- CTRMN042604-2626 Differentiations in Cigarettes Off Materials Other Than Tobacco Medicine Et Hygiene, No. 1216 [St Smoke From Cigarettes Made From Cytrel Contains Less Tar Than Tobacco Smoke and No Nicotine]
- CTRMN042627-2670 Advances in Modern Toxicology New Concepts in Safety Evaluation [St Syrian Hamsters Are A Valuable Option for Animal Experiments]
- CTRMN042671A-2673 Detection of Chemical Mutagens Using Concentration Gradient Plates: Observations on Results with 414 Compounds Toxicology and Applied Pharmacology, Vol. 45 [St Discovery of Chemical Mutagens]
- CTRMN042671B-2673 Dominant Lethal Studies in Rats of Five Hair Die Components: 2 Nitro P Phenylenediamine, 4 Nitro O Phenylenediamine, M Phenylenediamine, 2.4 Diaminoanisoic Sulfate, and 2.5 Diaminoanisoic Sulfate Toxicology and Applied Pharmacology, No. 45 [St Weak Lethality Results From Exposure of Rats to Hair Die Components]
- CTRMN042671C-2673 Motor Oil Antagonism of the Effects of So2 on Pulmonary Function in the Guinea Pig Toxicology and Applied Pharmacology No. 45 [St Motor Oils Reduced Irritancy of So2]
- CTRMN042671D-2673 Cigarette Smoke Inhalation Studies in Inbred Syrian Hamsters. I: Methods and Dosimetry Toxicology and Applied Pharmacology Vol. 45 [St Hamsters Exposed to Tobacco and Cytrel Cigarette Smoke and Results Noted]
- CTRMN042671E-2673 Cigarette Smoke Inhalation Studies in Inbred Syrian Hamsters. II: Histopathological Lesions in the Respiratory Tract Toxicology and Applied Pharmacology, Vol. 45 [St Tobacco Smoke Resulted in Larynx Problems Including Invasive Carcinoma Cytrel Smoke Resulted in Much Less Damage]
- CTRMN042671F-2673 Pulmonary Pathology in Rats Exposed to Marijuana Smoke for One Year Toxicology and Applied Pharmacology, Vol. 45 [St Rats Exposed to Marijuana Smoke Developed Focal Pneumonitis in Proportion to Dosage]
- CTRMN042671G-2673 Studies on the Pulmonary Uptake of Paraquat Toxicology and Applied Pharmacology, Vol. 45 [St Distribution of Paraquat in Rat Lungs Was Not Uniform]
- CTRMN042750-2764 Cigarette Smoke Inhalation Studies in Inbred Syrian Golden Hamsters Journal of the National Cancer Institute, Vol. 65, No. 3 [St Cancer Was Developed in Hamsters Exposed to Tobacco Smoke Cancer Rates Were Proportional to Smoke Concentration and Tobacco/Cytrel Ratio in Cigarettes]
- CTRMN042765-2769 Cigarette Smoke-Induced Cancer of the Larynx in Hamsters (Cinch): A Method to Assay the Carcinogenicity of Cigarette Smoke Progress in Experimental Tumor Research, Vol. 24 [St Hamster Experiments Are Valid Assay of Tobacco Smoke Carcinogenesis]
- CTRMN042770-2772 in Vivo Carcinogenesis Testing Toxicologic Pathology, Vol. 7, No. 1 [St Smoke-Inhalation Experiments with Hamsters Are Quantitative Assay Method for Relative Carcinogenicity of Cigarette Smokes]
- CTRMN042773-2782 Carcinogenesis in the Upper Aerodigestive Tract [St Carcinogens Such As Tobacco Applied to Mucous Membranes Result in Multiple Tumors Which Are Difficult to Treat]
- CTRMN042783-2787 Subchronic Cigarette Smoke Inhalation Studies in Inbred Syrian Golden Hamsters That Develop Laryngeal Carcinoma Upon Chronic Exposure Journal of the National Cancer Institute, Vol 71, No. 3 [St Smoke From All-Tobacco Cigarettes Caused More Respiratory and Larynx Problems Than From Cellulose-Derived Tobacco Supplement Cigarettes]
- CTRMN042788-2796 A New First-Generation Hybrid Syrian Hamster, Bio F1d Alexander for in Vivo Carcinogenesis Bioassay, As A Third Species or to Replace the Mouse Surv. Synth. Path. Res., Vol. 7 [St This Strain of Hamster Is Perhaps the Best Suited for Cancer Experiments]
- CTRMN042797-2800 [Comments on Slides From Effects of Smoke on Upper Respiratory Tract]
- CTRMN042801-2802 [Conditions for Approval of Publishing Findings]
- CTRMN042803-2810 [Disputing Ctr's Decision to Discontinue Research Chronology of Research-Related Events]
- Author
- Progress, I.N. Experimental Tumor Research
- Homburger, F., Bioresearch Inst
- Depository Date
- 08 Sep 1997
- Box
- 267
- Type
- SCIENTIFIC ARTICLE
- UCSF Legacy ID
- jot30a00
Document Images
/1
Prog. ap. Twnor Ret., wl. 23, pp 100-179 (Karisr,laal 1979)
Chemical Carcinogenesis in Syrian Hamsters :
A Review' (through 1976).
F. HowruROER
8io-Rtrsardt Instituta. CambrWes. Man.
COR1Cnll
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
I l. Sk in . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
111. SrEevunwut Tiuur . . . . . . . . . . . . . . . . . . . . . . . . . 10d
IV. CJt.ek Poucit . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106
A. MstAods. . . . . . . . . . . . . . . . . . . . . . . . . . 107
III. HiuocHattistry, Fim Strvt:utr., Cytolov . ... . . . . . . . . . . . . 110
C. Modifyins Factors . . . . . . . . . . . . . . . . . . . . . . . . 1 f t
V. Oral Cavity . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
V I. Tongue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 f
VIi. Retpiratory Tract . . . . . . . . . . . . . . . . . . . . . . . . I I t
Tracheal Instillation ot Cercirtowie Asenta . . . . . . . . . . . . . . . 12!
VIII. inhatation ... . . . . . . . . . . . . . . . . . . . . . . . . . . . 111
IX. Gaurointatinal Tract . . . . . . . . . . . . . . . . . . . . 146
X. Livc+ and Diliary Trttet . . . . . . . . . . . . . . . . . . . . . . . . 151
Xi. Kidney . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155
XII. Urinary lladda . . . . . . . . . . . . . . . . . . . . . . . . . . 160
Xl l l. hatute . . . . . . . . . . . . . . . . . . . . . . . . . . . . . I ha
XIV. Ovary and Thyroid . . . . . . . . . . . . . . . . . . . . . . . . . 10
XV. Taticla . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 166
XVI. Mamnury Gland. P.ncreae. Adtenal . . . . . . . . . . . . . . . . . . 166
Raferentxs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167
I TAis work .as supponed by USPHS General RaearcA Supc+on GrnRt SOtRt:.
03523 ( Cir.i.uon of ReuarsA Raourea and Faalitia). Raeard+ Suppoct Gr.nu CA 1 J Zll
and CA-1f/23 (National Cancer Instituul, and by Rio.Raearcb Coruulunu. Ine
Cy~ R t 1i f 7 '4..+* 4.G. 67'
a 1
CAcmiesl Carcinofenais in Syrian Hanatert 101
l. Introduerion
Hamsters continue to be important in experimental arcinopnesis
studies. Their check pouch remains a unique and most usetul tool. In some
emerjinr areas, their use is becoming especially fruitful. Such 6elds include
studies on renal ancers, induction of neoplasms and preneoplastic chanps
in the rapiratory tract by direct application of particulate carcinogens or by
smoke inhalation and urinary bladder araooIIeoais. It also bejins to appear
as if hamsters will become useful models for gastrointestinal arsiaosenesis
and for studies with inbred h.imstera, which once more make clear the basic
truths much earlier realized in mice, of genetic control of anoer suseepdbility
or mistance. Not only does every species possess its own pattern of mponse
to various arcinogens, but, within species, inbred lines diAa markedly in
their susceptibility to carcinogens. Sex is the only equally striking modi6er
of arciao=enesis. This genetic control of cancer susceptibility pertains not
only to diJfaent chemical carcinogens, but also to viral cancers (102, 193J.
Reslirstion of this fact renders it most important that the susceptibility or
resistana to carcinogens of inbred lines of Syrian hamsters be arefupy
studied and deSned, so that only susceptible lines wiU be used for screening
of substances for carcinogenic activity. The genedally determined diAereaoes
of carcinogen susceptibility also provide a tool tor the study of inethaaisms
of cancer production.
It is of jrat importance for the comparative study of various rsports
in the literature that the hsnutera used be clearly identilted in terms of their
source and genetic constitution. This is not always done at present, ta that
much published work, especially that done with sandombred animals, is
ditTicult to interpret and the results may not be reproducible.
The l;terature on chemical aranoteaesis in the Syrian golden hamster
was first reviewed in 1968 and 19ti9, and updated (tluouilh 1971) in 1972
(74, 75, 77). The Gterature sina then has betn monitored in part through the
use of DIOSIS, a computer-based information servia on the journals covered
by Biological Abstracts. Thers an now sulficient new data in the most recent
literature to warrant a further review to update the previous ones.
As in the first papers, the writing technique suggested by SiLYt wi11 be
used: The reviewer's summaries and evaluations of published material ars
printed in standard type, while the abstraets, mostly taken from published
papers, are grouped and printed in petit type.
To facilitate the cross-referencinS of this review with earlier ones, the
original order of main hcadings will be used. Throughout this review, the
~~`mR IMIN 042675
a 1
Ha+avsca 102
abbrsviations in the extnrae left column of the folloMinj list of chemical
arcioojens will be used. ~
A (I): Ilauf8)aethraesne
>f! (2): Sam*
(1): ba+ao(.)vyRM
DDC (2): Sam.
(1): 7HDib.are (a,r) arl+asoit
DBNA (2): Sanr
(1): NNiverodibuty4ntint
DENA (2): NIIWyl,/weitro.olbusaeaadn.
(1): N-Nivesodiethylamin.
DMDA (2): NEthy{.N-nivasaaAanunine
(t): 7,12Dimahylbeatl.kntMaases
(2): tamt
DMSO (1): Dimethyl wllosids (pnlmed) ot mtUhyl Wafoiide (altsto~tt)
(2): tutfmyteis(m."e.)
MC (1): 3-MahytdaiaetAnew
a: )yDibydrs)anahyfbensl i}MstMybn.
NMU (q: 1MahyllWAoWvrq '
v a):
a): MMe1AyLN~aitraouns
Wyl ~
NNHMI rn:
(1): Sam
Haahydre+aia~d N4s
epift
(2): Sanr
NM (I): 4-NivaamoPholim
(2): Ikm
NN.v
Nt (a:
rn:
(1): 1Duty4l-aitrnaaan
NDuryl.N-mvaau..
tNivaopioaiditr
(2): Sanr
DMN (1): NNivewOimeNylamine
(2): A~Mahy4Meivaometa.auaias
DPPt (1): NNitraodiyropyhn+ias
(2): NNitraoN-qropyFt ~rop ~eartiia~
MTN (1): NMahyLNrtivaop~Dpyl .nwr
(2): NMaAyi~Ntivaal -prop aaamias
V' I b R / l N 042M M' . 6
.
C
a
Chemful Gre;nopenais in Syrian Hanum
D!N Dupliaa of DDNA, abore
2HPPN (I): 1{hopylnitrosantino}2-propanot
(2): 1{Nivosoyropyla mino}2-propanol
DHPN (1): 1,1'{Nitrosimioo)di-2-propanol
(2): 1,1'{Nitroainaino)bis(2-propanol)
DMDPM (1); 2,YDimeNyl.)V-eitror:octipropylamine
(2): 2-MaAyI-N{2.a+aAylpropyl}N-nitrao-l-txooaaamier
/k
103
(1) Narna,ocordiep to the rvMr of oTpr+ie eontenelaure of the Istt,reatio/al Uoioa
of Pure and Applied CTKmiutry (IUPAt7; alr.o G4mie.l AlrrF,reu aamr for the
!xeriws (19t:7-: ^ 1) iods+t period.
a) Caaeia/Abser.ar, nanr ror tha erareat (t972-1976) indes pariod.
Tse author paufully acknowbd{es the kind o8ioa of Dr. Kuar L Loomro,
Die.ecor of Noma+clature, t3ea+ical Abstracts 9erviot, The OBio State Ueivasity,
Cotumbus, Ohio, in trompilina this list.
11. Skin
While La et al. (101] had previously reported melanotic skin tumors
with a single subcutaneous (s.c.) injection of DMBA to aewbora haansters,
Auaatf er al. (10,11] observed similar tumors after single iotratastric(i.6.)
doses of DMBA (20 rnS(100 6 body wei jht) given to male or femak haautea
ajed trom 6 to S weeks. They observed a significant incnase in the oumber
(but not size) of tumors following pinealestomy. This effect of ablative
pineal surgery wu more marked in males than in females.
ln our own studies involving s.eL and i.g. administration of DMBA,
we have never seen mdanotie skita tumors. The description of AuttatT's
melanotic tumor so closely resembles that of GtUm er al. (1. oata. Caaar
Inst. 40: E67-t77, 19681 that we are tempted to spexv4tt tAat pottsibly the
hamsters used by AuntxT's group earried the GmlG vinu, wbich atay have
been activated by DMBA. (Glum: ?umors arose by proliferatioa of hair
follicle cells, usually those of the ha.ir route epithelium...'; Auaur: These
melanocyta proliterate intensely in the derma which etuJoses the hair fol
L'cles, at the expense of which these tumors appear to be born' (reviewer's
translatioop. AeocptinS this assumpdon, we would then postulate that no
such skio rumors are induced in B10 strains because they may be free of
Gral6's virus.
0
0
PT
C T R I I N 0 4 2- 6 7','r'q
HnrtVROa 104
At»[RT H.l. (I0): FortyeiBht hous after pineileetomy (or eh.im operatioa. or no
trntment). Syrisn aolden hamstcrs (I1-43 eRotti-4 animals per Broup reponed) reeeivb
a sinpk dots (by gastric int6bation) of DA!!A in 'Labrafil 19a0 GS'. 7.5 ma/100 e body
treatht. Sacri(ioe was made 13 months a(ut thk trcstment. Melanotic tumors apttand
as early as a months sthor treatment and varied fran I mm in diameter to 2-3 em in
diameter. The authors eondude: (1)'fhe adminiseration af.a single dose of DAtBA bs
stomach tube indxa Ain mds>,otie tumor>i ofthin 4 atonthe i>t n+ale and in femalt
hamsters. (2) Pinesbetomy :eaaato ooeuidecspy tAe aumber ot the thae tumors, but,
pinolatomftatd famaks produce kwer melanaie tumorta {hsa tnales. (3) linealsctoe7
sRaeu neid+er sist nor histological appearartee of thee tun+ors.
AuaRt sr of. ( I 1): SinSle doies o(DM LA in LabraRl (1l44 CS) ~rers Biven to male
and female Syrian Bctdea hanuur>t at 6-i weskt<of ape. The dow varied from a to 33.3 mS/
100 B(wdy usight, but dosea above 20 mB.r100 g e.r. were found to be toaic. The animals
wsre ssaifieed Ll3 momha beyond thia treatment. 1Khile aintilat utatrtKns with 8A failed
to produae mdanoue tumoea and no eueG tumora aert e.ea in 37 hamsters or both t;aes,
all DMBA1rn+ed aninub had nrctanotie tumon. The bum finr (3.t.months) and the
number of nrianot+: t.mon were proportional to the do.e and a function of the length
of the observation periid. l.4ost of thaa ttamors wsre unsll (below 1 mm dianwer). s few
were larp (r.erd oa+umeurt); they were Iraniptantabk growb+i alowly and never
metastasuins Aleer reketion of tueh tesnsplantabb traroors, thees veas no rsatrrsnw.
Thers .ere so tra tWTerenm A fsr aintilary v..ud p.nitlly a)biso' huenteas (sero.
tnclanio .Nts') .W dnelno.d ntdanotle ttanoras. Other tunaa observed in hamsters
fotlowin{ sin{b do.M d D M BA were se6.oaota eyas, erib of th. o.ariea. iplcnie taiorr,
adrenal tumon. pwe epiUtdianae aud eta+atatr sdeAOaroeoetas~ HietoloBiaUy, the
enelsnNie tumen wi dewribsd rs benipt.
Lu sr.t. "01(: T1w paper re0oro *ert tba to 1at tbe alf.etirer+as of DMBA
when Biva+ ia a uork inpetion to the trwboett bsa>st.v. rat and e+ouu. Careinoyen was
sdminister.d in v.N-opr7lin (Trioetanois) trom Eastman OrpAic CAentinb. Nw York,
N.Y. The ttot+c>nstrauar ef DMBA ware weA tAst the artaunt of wlvent was 0.03 ml.
Daes of 1.000. 200 and 100 vi produced subaLneoul sueomas and detmsl e+dano-
tytomst. Add;tionapy. a slight aooderaAon of the apporana of maliBnuu lymchoma
.vat founJ. In comr.-.b in Ut. Swiss and AKR txrainr+ of mia, then wen tumon distant
from the applia.toe sita namdtr. fMepitansa and hatB adonomttr la the case of Lewis
nn, there were asenually local ranaro. T!r mioraas and ebs e+elsnocytonus iodueed
by Qw praeedure were sion;lar ia appearanw and ntivnaoopr to thoee induced in adu)t
harrote>s.
111. 3"6curaKaw Tduus
Sueomas of tbe subcutaneoua tissue have been induced in Syrian
hamsters with MC, 8P, Nnitrosobutylurea (neurosarcomas), DMBA and
atetals, and the pro.M c)vyacteristia of induced tumors in transplanu and
tissue cultures as wrll as thrr ebromosornai properties have been studied.
Various nickel a+e+pounds and titanocsae dichloride vwert found to be ar-
~'°''~~~ 042~ -~ ` S
CTR
/1
,
1
Chemical Careinopena's in Syrian Hamatcrt tOS
dnojenie. Sarcomas induced by BP in the mature oRsprinj of hamsters
injected s.c. on the second day of pregnancy with Freund's incomplete
adjuvant appeared earlier and frew more rapidly than did similarly induced
tumors in the offspring of uatreated mothers.
DIP.oto rt.l. 127): Sia primary subcutaneous tumorz induoW aith a single inj.pion
of at' or DMBA were analr:ed for hiuopstholow, growth in rirro, tnnsptanubiliq, and
karyokKy. All tumon usn bbraueomat with varyint degrees of diRaauiation. Tunrot
wltueas wae ehuansrited by rapid growth and inarpfs in acidity of m.diuen fotb..d
by quick dsperwatioo and wrvival ot a fow a1b which produoed a population that gw
indtelinftdy in Nrnt. Thr initial populations wen diptoid. twr diploid, or taraploid aed
Aad some aantrie pieess, chromatic rteananacmonu, and nsarts ehroerowm. hut
aithout any eemmon karyotypic cAanae. Subaet{uentlY. Aeteroploidy incotaaed. Ctitt
Leked orioetatioo and oorasionally piled up. CGoninp without a l.edv taW- a+d is dinraa
adoniee, some of which were randomly orieaued with eriaerotsinp of R4ntents. Tunton
derFvtd from tbeu wlturn
.at trampiaenblt iato I+anwen Ttwe prnors .w mor. .
anaptastie than primary tumors. Cempariaon of thae studies with iu.1mn studies in which
quantitative tramtorn>,tion was obtained with Syrian hsmstp tnnhryo edb and polyeyeli0
hrdroarbon carcinogens hads to the oa+dution that is.rtn inveatiptions of tramlotttr.
tioe pro.ida information rekvant to In d.o tranuorntatbn. (Authon' atxuact.)
Ftmsr and ScMUuoa (441: Groupa of random-bred hansten or t>oJt wea wsighini
l0-73 a were given monthly inttumasvlsr h+janioro of nieksl po.der, ttictdaeset or
titanasne auspa+dsd in trioctanoin. Tramptantable dbroareoenas .en induced in a low
ptxcsnup of the aaimab that received nietd po.der or nictdooane. la oontraa, higher
twwr ineidcnoet wers observed in FocAer-3N nts. Genvatiutipts drawn (roat a tom-
patisoo of inbred rats with random-bred hamuen ans probably not valid. lnbnd ardao.
een-wseeptibk lina of hamuen ought to be studied.
HorwaoU a.1. (79): Single s.t: injsetioer Mt triraptrlia of 300 µa or Ait^ or Dp
or DMBA produced aa sareoma at the injectiat tit+ of aeou rou.d inbeed aralna of
Syrian hamsters. DA produced so tumon at t!r injaetien aitet Iw.e.+r, io twe inbnd line
(S10 t7.2o) 10% of the trnted fatuM developed broeehiotar adenomuom.
The nte of tumor dcveJopnwtt and ths twraber of twnen .an.d depending oa tJ>e
inbred linez For all of the taud arsinopens, the same theee inbred t"ina were teora
auaoeptibk than mou of the other finea teated (B101c7-210 310 i3.3, 210 1S.1i). Fwdint
of MC awed ardnoeus of the purointestinal trael, fsmale rsproduaiva USM aad
mammary {Iand is sia inbred tuw and ons randomly bred tine o( Syrian hantnera. Whaea
in thM randomir bred tins the newltt wn aiawtu te those rsponed t+rerviowsly by aUA
Po.rt. the incidsnes of a{t wtnoes varied widely amon{ inbred sulifr, tlt" rnv.rlina
dut penetie factors eovern the responses ol Sy+i+o paatems to arcrwecnesis by patrie
intubation of MG Geneties appcu to determine the napaui.enes or epvsppui.enaa
in penerat of inbred Syrian hamsters to carcinogenic stimuli. Knowledge of thos rh.it.d
.arubls susceptibilities makes potsibtt tbe ntionaJ ntactioe of inbnd ti.ef that ate hat
suiud for artain atperiments. (AutLara' aEatraet.)
(A.nwa.u and Surirct (1111: NNittoso0utrturn iejacted aelly is. in 1% ethyl
akohol a a doae ot20 wNt body weiaht, beginning in 7.day-old hsmuert, eautsd 12 aanp.
tarsomai in 21 surviving animals so treated. Nona of these twnon, which oacvned at
the inj.ction siu, rnembkd the hunun m7zoid type of neuroacnie saroono,
CTR f f f 7 0426Yi 9
i
W
/1
106
Popest:V and GXoe. 1l)aj: tumour pdYRssafe driputer a tnroplant{tion
method trsed on the repeated and xheduMd interruption of tumor graft with the purposa
of in8uendng the develepment e( trophic phenomena and the relations bxtwesn tumor
implant and host. hrimary tumee>s induad by )-nethykholanthra+e in polden hamster
-e cyto{snetiaatly atWyaad after monotoie monoatrie oolypruie (6 times ia at t,
intea^.b).
CAromaontal constitution af tM tumow which did t+et underso poty9assap was
seersploid. Follonrin= the polhpastap of tbe pdmuy tueow in anogenek taolden hamste
of oppaia as, twr diploid and nornal diploid cells of the boN wat pndominant. T'he
significance of thia nadihation is disatm.d u related to the Inuewne reettonse of the host
to the uadifl.d propenia of tAe tumor imtsfant by polypawae. (Authon' apstraet.)
IV. Cbeek PateA
Studies on the eheek pouch may be divided into those dealing with
histology (including fine structure) and histochemistry of developing induced
neoplasms, and studies concerned witb modifying factors of.arcino=enesis
at the eheek pouch site, indudin= experiatental radiotherapy and chemo-
therapy (E2) of induced lesions as well as ae of the pouch for the testing of
suspected carcinogens (34, 193J. DMBA, the carcinopen of choice in these
studies, was ta:ually applied aa an 0.3% solution in puaQtn, aatone or
'Orakisse'. For weaker arcinotent, a technique was .uuested 'which en-
e:oses the test material into selatin capsules and polyethylene sheet for
:radual release and repeated replaoement 1151},
Fine structure studies reve:aled the formation of pt+eudopodia by trans-
fortnin= epithelial txlls which wete no IonSer d'Win=uishabte at the onset of
Nistolo=ially reeolnirabk cancer (1911~ NMU was also used topically and
introduced rhabdomyoblastornas in 32% of the treated animals, and sastric
tumor in 44% (1931
Studies on the early Gght tnicroscopic changes uen in DMBA arcino-
Senesis in the vascular elements of the cheek pouch show that neurovascular
changes in the terminal vessels do oeau extren+ely early (25,26). Studies on
the inflammatory response to DMBA showed a steep and steady rise of
maerophsM concomitant with tumor development (44 Some of the histo-
ehemical techniques for aryl hydrotylases trvcaled a particulate rnction -
produet in epithelial alit, and some of these partieles possessed properties
of lysosotnes. Changes in siss, ttaininS properties, number and fragility of
the lysosome-like and other ptuticles were observed in arcino=en-trated
epithelium before any histological or cytological evidence o[ premaliinancy
(172, 173). Changes found in human prernalipunt oral lesions resembled
4j TR I , I V' 42;sM 1+* -..d
4
t:Aanieal Csndnoeemis in Srrian Nanwe+s to7
those found in preancerous lesions of hamsters. During the course of ar-
cinoSenesis, marked increas.s in DNA content in basal and parabasal cells
were observed (14j and DMBA !Jnjutated DNA synthesis in an increasing
number of cells (192j.
In exfoliative cytology studies during arcinosenesis, typical cells were
found in the earliest erythematous lesions (40j. In the premalignant stau,
pseudopodia =rowin= into the intrsepithclial spaces were observed (1991
In malignant basal cells, the total length basal ttsembtsne was inasased
and the total lengths of desmosomes and hemidesmosomes were decreased;
this may be associated with greater cell mobility (t961.
Fine structure studies revealed the formation of'pseudopodi hy trat:s-
tor+ttia; epstl;eliat oslls which were no longer distinguishable at the onset
of histolojially recognizable cancer (19d). NMU was also used topically
and introduced rhabdomyoblastomas in 32% of the treated animals and
gastric tumor in 44";.
Modifying factors of arcinopnesis (or of established, induced tumors)
have been studied in the hamster cheek pouch. Such factors include chronic
irritation and trauma (170j, metals, speci6ally zinc (13E), castration (103j,
hormones, testosterone (132j, cortisone (13Sj, cortisone derivative in DMSO
(171j, vitamin A(132,133j, vitamin Ds and Da (fS7j, antilymphocyte urum
(46j, and bacillus Glmette-Gudrin (43j. Therapeutic a=ents, such as X-rnys
(t51, and chemotherapeutic agents (cyclophosphamide, metbotreute and
vinbtastine) have also been studied (106j. Chlorpromazine also was used to
suppress urcinojeneLis of DMBA when applied to the eheek poucb prior
to, or with, the arcinogen (103, 1341. Human saliva, on the other hand,
did not protect against DMBA arctinojtrtesis (1l9j. The effects observed
with various moditying factors are summarized in t,abk l.
A lesion described as'lyrnphotaalike' was induced by three times weekly
application for 12 weeks of vitamin A palmitate in liquid para/firt (20% w/v).
Theu appeared to be chronic inAammatory esudates rather than lymphomas
(104j.
A. Methods
Ramaeru. 1131) (w al.e pp. It!): A lachniqut i1 deaeribed for Mltina uepaeud
earttinoyrnio wbwnce in tAe twrota't cAxsk pouclt.lt awuiau in iftening into tM d+"k
poucha pani.llr Aeatlealed polrethrlens beg containing ta1 iubuance in multiple gelatin
eapsuks. It b espesuly witable for wnky careinoSenic tompounJr tlut nuy npuin: the
full Ws span of tAe u+snat bslon sfttusa elLnps. The nuut.dsnuea ars simplicity,
k
Lr t R i i N 0"T 2 f..A Si. JF .11
I- .
HoM.vacea
108
Ta6/e I. Modiflinp faaon of arano0setesh as uudi,:d ia tAe hamsw cheek poud,
with DMBAinduoid neoplatnu
1-_
Substanot studi.d Routs At what ape Efact obeerved Reterena
Ch'ron'r if. italia..
`I
tsrcinoGen
BivCR _ .
0:!% DMBA 7 per top;r d i momt.. .one
wek plus 3 nar
incision at 12 weeks or
Rtanipuladon of tissue
Zinc
0.5% DMBA 7 per p.o.
week for 1.eeks Zn In
tkinking water;
1001>0m in addition
to 21.9 ppm in dist
Hormones
Gstration 2.eeks topins
before appliotan of
03% DMBA ie
p.arsAin each week
for up to If ..eks
7stoeterone: nurs- LaL
lion of inuKt nuM
hannten, I wak
before^3SC CR1BA
sns applied 7 pa
e,.ek (9-12...eks);
! 3 n,e or tstosaron.
propicelay
'I.nL 2 K per.eek
Coniwne acesate: topie.l
DMI3A 0.3% in
osnRm I pw.esk;
oortisone 0.05%
applied sinwltarrously
for 12 weekt;
7riamt:inolone
Wlirors~I I d, Ifd 11
21resMrdroryvrep+.-
l.r-dierm 1.20 dionq
In DMSO 0.023'ii topical
painmed sinwltansoury
srith 03% OMBA
in tminasl oil
170
yptnt nv,rked reduction 138
of an:inot,enab;
11%in23w.eks
instesd of t7'/, in
9 weeks ie controls
1-1.5 uo effect on start of 103
trontbt arc:noBensan; wnr
dowing of tumor
Vrow11 and deeRaw
of numb.r of tunocs
13-2 !n intact euk 172
awmlr aniattls, wto
uerom d.arawd
oreinoma
fatmlios .
1S-2 Fn DMBAdreatad 1?S
ntosUt snirnas 3.0 tuews
pr troatad poucl;
with eonisone,
0.(+ tunan per
vaud ooucA
d moatbt no eAect (probably 171
eeaust with DMSO
the apent diaappean
rapidly from site)
,
I
CY! R 1/ i V' I ti m v M V' ti/ 2
b
Cltemieal Carcinoienesn in Syrian Hamuers 109
T.N.I (eant.)
Substana uudied Route Atwhata{c EBanobser.ad Rafersna
etteinoptl
iivta
Vitamin A
Vuamin A (oonoen-
asuioa tatspec;fied)
Orinted topieslly
with 0.3% DMBA
tot~ 2 atoe8e; aeaefar.twn ef (w tYo ttut
Vitamin D, nd D, topidl 2-2'/,
months
AatilympAacyu teram
Caxinopn DMBA intrs 3-4
0.3% in Navy proritAnrl wionthf
enineral oil AL.S
0.13 m!
Lytowtie aBenta
DMlA 0.3'q ie topial 1.5-2
prrsfRn; months
CyclophapAamide
) S%
Metbotrwte 0.03%
Vinblutine 0.0223/.
Ca{oryrantune topeal t
Baeillm Calmtxt+wGufrie tysteteie t
ttunor focmtttiar Wnr. (32)
!ae etor~
rewoot OaPv)
132,131
inAibi.ionoi We+a 67
farmation
..rlier nnd mors ri
traquaU tumors
with nrxt malrpVnt
cJuraeterittia in
AWrated lumstaf
106
qwtutteablt tua
prest;ioa of earoneBc+tesit
vuatia+.b+e «nr
Oeetiion or e~rw
PM*
marked utRibitiee
of arcisoPa+tas
following pretrtas. 103.134
nrnt er S itA rin.u.
tan.otr trtatenK
marteA iMubn,oe
oudnoet+te.
or
10Aibiti0n of .3
nrcin 4ene+:
C T R. M N 0 4 2- 6 8~`~
