Council for Tobacco Research
[Manuscript on Strain Differences in the Response of Inbred Syrian Hamsters to Cigarette Smoke Inhalation Submitted for Approval to Publish]
Fields
- Depository Date
- 08 Sep 1997
- Master ID
- Ctrmn00041967-2810
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- Author
- Homburger, F., Bioresearch Consultants
- Recipient
- Hockett, R.C., Ctr
- Type
- LETTER
- SCIENTIFIC REPORT
- Box
- 267
- UCSF Legacy ID
- jnt30a00
Document Images
Berafald et al. Pajc 9
Organ wei8hts were determiaed in a certain aumber ot esses.
Sernm tsi8lycerides by the nnorometric teehaique (8) aad.irus
prodiesT were also studied in some =nt-tst of each sroup.
7 By eoartesy ol Dr. Robert J. Huebaer, National Instltvtes ot Health. )
RES ULTS
1) ).4ortility: As shown in text-n;uses 1 and 2, mortality
was very low in all groups uatil about tbe 60th weelc of tbe esperiasent.
at which time the a-ir-na1s bad a ehronolo8ical age of appro3dtsateiy
73 weeks. Tbsreatter. mortslity increased rapidly in all aroup.,
reaching 100% at about 100 weeks. Neither smoke e:posure nor sbam
smokinT bad a signi_icant eL~ect oa mortality. There was no dilierence
in sur vi.al betweea the 2 strains.
2) Chan¢es in body wei;bt (table 1, text ti=s. 3 aad 4): Ia
both lines of h,amsters, individ::al body weigh_s were altected by emoY.r
Lahalstioa aad, in adltion, by the mere experimeat.al maaipuLt. m..
sucb as sbaas mokin8 cooditioas and/os stress piodrced by the latzer.
Initial weiabt Ln both groups averaged 108 8. Tbe BIO 87.20
case-held controls attaiaed a litaal weight of 144.3 8, whereas the
BIO 15. 16 aaimals attained only 325. 0 8.
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~ Includiag only aniriais saczificed for_lsistolo'gic saidies.
.1 .,Itean valuea: staridard deviatioas in pareritheses before
I
i the_s_1_a_at; ni:mbers of animals in pareutbeses altei the
~ Statistical aigniiicance is at the 1!', confidence level (p t 0.01).
3 ualess the value is set in pareptaeses to indicate significance
at the 5% contiderce' level only (p c 0. 05). When no t-value
is given, diflereace is not statistically significant,
Insufficient data.
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Sernfeld et al. Page 11
I
Esposure to cigarette smoi.e reduced body `eight of both
iabred stzains by about 10 8 during the first 2 weeks of treatzannt.
Subsequently, weigbts Increased aisin. but socnewhat more slowly In
BIO 15. 16 a.nimsls than in BIO 87. 20s. Because ot the low final
weigbt at cagebald BIO 15. 16 bamsters, the weight diCierence
between the controls and ..taoke-exposed bamsters was much less in
tbe BIO 15. 16 llne than In the BIO 87.20 llne. Sham smoking prodoced
body weights intermediate between those of tLs caQe-bsld conQola and
tbe emoke-e:posed animals in Line BiO 15. 16; it had no eaect on
body weigbt in lLne BIO o7. 20.
I: t`'.as appears tha: the long-term response to smoke
iabalncion, i. e. , the Sailure of the smoas-ezi>osed aaiasls to ;ain
weight. was due. at least la Ltrge pa.rt. to direct effects of su:oie
L.y31ac1oII ratSer tLzz to nonsxci:ic s::ess.
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11225522
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Bernfeld et al, Page 12
3) Garbon Monoxide Content of Blood: Baa.eline levela of
earbozyh.moglobla ranged from about 0. 1-0. SX.. Lmmediately after
erposu:e of hamsters not prevlously fahallag smoke to a sequence of
20 pntf cycles of smoke. carbozyhemogloain levels rose to between
20 and 407.. Within 4 hours after ezposure, these high levels fell to
4-1PXi. A second exposure on the same day again raised the Level to
30-36YJ.. After two 20-cycle exposures to cigarette smoke within 4-S
hours an tbe same day. and 13-19 hours rest dnsing the nlgy.t, the
cazboxyherno¢lobia had returned to near pretreatment levels in aL'
tnstsnces.
Frors these res:~lts on a.nimais not Lncl;adec in the c'uonic
iaha1ation study, it was concluded that exposure of hamsters to cig-
arette s=oke for a-:_ch shorter tir.ze ,xriods, i. e. , to d pufi eyclea
tarice a day, as La the chronic inhalation ezperiment, e-iay tbus be
aasuzned to cause no LastinZ acc=uladon of carbon acoozide la t:e
blood. This was actually coafirtned 1n 22 hamsters after 13-45 weeks
ia the chronic study. Mea.o blood carbo:ybemoglobtn measured oo a
Monday morning before the first espoeu:e to amoke in5a:ation of the
week ranged from 0. 2-2, 0"f,, with a mean of 0.63j..
CTR Coh(TRRCTS 005?82 Z
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11225523
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Bernfeld et al. ?age 13
4) Cbantes in sertian triglyceride levels: Sernm triglyceride
le.ela, dater:aiaed after 45 useks of smoke t.+a.l.Mon or taalat:ining
i
control conditions, ranged from 145-222 tas/100 mi with standard
deviations fsom 28-9T m='J.. Because of tbsse large iadi.idnal
rariatfon. (staadard de.iatioaa), the dlitereaees were Ls trom
being sigaificaat. Accordingly, t+sitbsr smoke euposure nor sbam
stioidnZ prodneed changes in seram triglyterides.
5) Virus profiles of test aniaals: Tables 2 and 3 su**+=arize
the virus profilss detsrminad at 45 weeks in 6=u+*++aLa from each of the
esperimentai groups and in 6 youa=, uatreated azlimals of each strain
which corresponded ia weight and age to the bamsters at the begiaatng
of t)3.e experL=ent. The data clearly indicate that the virus profils is
not cbaaged by smoke exposure. sham smoking, or prolonged cajinl
=der the coaditioaa of t.e ezperimeat.
6) L1fluence nd smoke exposure oc organ weijbts: 3ecaase cf
atraia diEterences ia body sise (table 1) and the weight changes r: oduced
by the esperimeatal procedures, absolute organ weights in tLese aaimals
were diflicult to interpret. Therefore. only relative organ weiYLss were
used for analysis (tiblee 4-6). Welghts were tabulated ouly for tbe sacri-
ficed aaiasala, not for those dying spmtaaeously. This was done because
changes in the respiratory tract were of tae greatest inurest relative to
smoke earponue. and inclusion of :he lung weijhts of dud hamstsrs would
have introduced a.arlable and uahown amouat of aZoaal pulmonary coa-
jestion and pulmonary edema into the a.era;es.
CTR CaHTRACTS 005783
11225524
CTR HN 042"4422
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Group
Desig-
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- Tible2V .. . .. .. _.
_ -Virus Profiles in 87.20Ha-^.iste'rs attefi-
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Virui _Profile in Individual Himsters
:
: Bera:eld et al. page 1} -- -
;
TreaL-nent of Animals
yy-
Complerrient-F iixatio`a ;
- Test
RRR
_.-
In Serum
Hernigglutini ;
tion-Inhibition
- Test*R --
PVM
Sendsi
i
D Smoke Exposed 1:20 1:20
11 n ~ 1:20 1:20
11 Y ~ 1:20 1:20 .
11
1:40
1:20
11 1
1:20
1:20
II
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1 1:10
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./
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M. Ad,
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0 0 Tr
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t Except anirnals o( Group FF which had not orevit.usly been under any
s
..
s.
perimenta1 conditions.
Each line represents one animal.
RCV, rat corona virus.
ex-
GDVII, Reo 3, K. Polyorna, MVM, KRV. H-1 SV5 and Ectromelia tests
were negative in aU instances.
Abbreviations: PVM, pneumonitis virus of mice: M. Ad., mouse adenovirus,
hSHV, mouse hepatitis virus; LCM. lyr::phocytic choriomeniagitis virus;
cTR caN-rRacTS oas"(8Q
11225525
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- ~-,6Viius Profiles_ ia 1S.'16 Hamsters'~
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1:40 1:20 Tr
1:80 1:20 T: Tr
1:40 1:20 0
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1:20 1:20 - i - T: Tr `
1:10 Tr
1:40 1:20 0 3 2 ~
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Except animals of Group CC which had not prr.ious:y been usder a=y
experirnental conditions.
Each line represents one anirnal.
GDV II. Reo3, K, Polyoma. MVM. KRV. H- 1, S%'i ana Ectromell-a tests
were negative in alll instances.
CTR cONTRACTS 005785
11225526
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~Re.Iative_Spleen Weights ~of Hamsters
-=Saeiiticed for W,sto ogic S udiei :-
Leagth
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~ .. .. : _ .
!Sta.tisttcal Sigaificaace of
f
of
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"
"
= Exptl.
r EuptL
G Coot:d 1
I
ondi- Line e E
posed
Smo rtoked
S
rn-S ~Ca e
HeId oup
G roup Verszs
Control Group- Control Group _ Versus Versu. ~~rol 2
(Weeks) (Exptl. Group) (Control 1) ' (Contiol 21 Corihvl 1 Camtzol 2
ial (bl ~ () (a) .., '(e1~s=Y' (t) (g) (hl
40-60 15. 16 7$:2 (18.56/6)
I 69.8
(349/5j 81.2 (1i:97/6) - - (2.Oi) ,
60-75 " 170.0 (98. 14/6)
- "( =' (-~0) - - -
-5-90 " (124.2 (31.51/24) 116.9 (71.81/f7j 116.6 (45:98/11) - -
>90 " I 141.6 (55.78/25) 135.0 (48.24/8) 117.8 (41.23/121, - - -
40-60 87 .2'J ~ 540 (16.43/0) 62.0 (24.30/7) 83:7 (18.00/6) !j - 2 (1-80)
eJ-?5 " 83.4 (14 50/9) 92 8 (32. 28/13) 185. 1(107.94/I1~ ~~ - 2.7? 2. ~4
5-c0 88. J(19.52/22~ 69. 5 (3J.61/6) 106.5 (25.63/17ii ! - 2.E2 -
103.0 (-:4. 13/3C l1?.9 (36.85/12) 110.9 (38.25/7) ~~ - - -
..
Absolute weig=ts, divided by individual body weights (in
multiplied by 1C0.
Including oa:y ani.-nals sacrificed tor histologic studies, nct i:.-
cludiag aai:Zals that died spontaneo_sly.
!Mean values: standard deviatioas in parentheses before the slaat;
a,:,.-.nbers of asirnals in parentheses after the slant.
j Statistical sigaificance is at the 19o confidence level (p s0. 01),
ualess the t-value is set in parentheses to indicate signi.ticance
at.the 5%6 coafideace level only Cp s 0. U5). When no t-value is
givea, Aiffereaceis not etatisticaily significant.
s lasutfi cieat data.
CTR CONTRRCTS 005786 °
11225527
CTR HN 04~ "449,
I
i
i
i
I
t
.,
.~
i
agth
Ls ag th :~~
~~^V:r~
~a.~'~,sy;r~~
~,. 3. .. V -, . ,
StatiiHeal Sig'fi f
at eancs o
,
of ~
-'?>=s.y;
-
es betweea 1.Sea.ns
Diffe`renc
'~
Tirne In- '+t_.
Relative Heart Weighti~ .of H amster. oup of Sasne Ia-
lof Tao Gr
on bred -~= _(Milligraaii)
e`; ~(t=~Iolue.
Ezperi Ham-
mental stez z {- ,
i
"
" Expt1.-
'-
G
o Exptl.
G
p Coesrol I
Condi- Line Sruoke Exposed ted
Sha:a-Srao Cage-Held . up
r rou Vstsas
tioas Group Control Group
' Control Grbup 1 Versus Versus
2 Coatrol2
(Weeks) a (Exptl. Group) l)
(Coatrol (Conaoi 2` ~Contsol I Co:Sro1
(a) (b) ~ (c).. . _ (d) I (f) (g) ' (h1
40-60 15. 16~ 407. B(28. 87/6) 348.6 (16. 06/5) 339.8 (36.91/6) ~ 4.07 3. 55 -
60-75 " 494.3 (57.89/7) - (-/!). - (-/0) - -
75-90 " 448. 5 (128. 5/24) 418.8 (74.84/18) 417.0 (79. 86/10) - - -
>90 " 574.0 (132.5/25) 439.5 (82.95/B) 44=E (53.83/12) 2.69 3.27 -
40-60 87. 20 407. 8 8 (57. 95/6) 336.9 (21.65/7) 326.5 (26.?5/6) 4.67 I 3. 13 -
60-75 " 437.7 (26. 10/9) 415.4 (86.43/14) 377. 7 (3&86/11) ~ - ' 395 -
7i-90 " 1477.4 (63.57/22) 468.2 (74.44/6) 422.4 (84.67/17) -
f,l i -
> 90 ' z163. 7 (62. 55/30) 44 1. 7(82. 04/12) 4:1. 7(22 Oe/6'~ i
j - i ' -
:
a
~.'.r *
j-if
-"~Y Z { ~ -
~-Sacrit1ced for Hiao_og c u
3i--..-...r~,r,-.s~
Absolute weights, divided by individual body aeights (in grams'.
mult::lied by 100.
vfean values: staadard deviations in parent}:eses before the slaa::
nurnbers of aair.tals in parentheses after the slaat.
s Statistical significance is at the 1^% confidence level (p s 0. C1),
unless the t-value is sst in pareatheses to indicate significance
at the 5% confidence level only (p s 0.05). When no t- value is
given, difference is not statistically signitican:
:ncluding only aaimals sacrificed for histologic seLdiee, no: i-
c1uding ani:rals that died spon:aaeo_s1y
! Insufficient data.
CTR CC~ITC~ACTS oo5~e:~
11225528
4.J I m I ` 7 7 7 4! 0421' I LdY
_
BeTZfeld et al.
_~_..
page 18..
L`+
:Tabls 6:
(
I
Absolute weights, divided by individua] body weights (in
mul:ipliec by 100.
Including only aarnals sacriticed for histologic studies, ntXic-
clt:ding animals that died spontar.eously.
! Mean values: standard deviations ir. paren:heses before the sla:::
numbers of aniraals in parentheses after the slan:.
Statistical significance is at the 1!9 confidence level (p s 0. 01).
unless the t.value is set in parentheses to indicate sigaiticance
at the 5%% con.ridence level only (p s 0. 05). When no t- value is
given, difference is not statistically siYaificant.
s Inauificient data.
CTR CQNTRRCTS1 0a5{88
11225529
_ 'Sacrificed fo
r HistoloYic Sttidies -
z. . ~- ~ ° . ,~.:- - .
g:~' ': "
Relative L_aag.W_eighti*_of Ha.maters
'
Length
f
:'
;;
:
.
~
o ,
~
~;
^ ~ p
feiea
ces between 1+Meaas
Time in- I Relative Lnng Weights+.of Hamsters**t ~ of Two Groups of Sami Ia-
on
F
i- bred
H ( (h,til3iiram.) Z breid Liai, (t-Values)i .
sper am
~,
~ 1
~'
(
taental ster . ... .. . . - . . Erptl. EzptL
~
Condi- Line ' Stnoke Expo.ed "Sb.a.ta~Smoked" Cage-Held i Group . Group Versns
tions
(W
k Group
~
E
' Control Group
1
-
o Control Grot:p
' ° I Versus
t Versua
C°0G~
ee
s) (
zptL
Group) (Contr
)
l (Control 2) Con
rol 1 Control 2
(a) (b! (c) . . (d)_ ...- (e) ~ (f) (gl (b)
40- 60 15. 16 : 976.5 (62. 19/6) 1079. 0(49. 80/5) 827.3 (191. 92/6) (2.91) - (L 83)
60-75 " ; 1701.7 (488. 0/6) - -( - /s ) - ( - /0) I - - -
75-90 " 11166.6 (240. 9/24) 1259.2 (290.2/15) 1283. 2(233.1/11) I - . -
> 90 " :1403. 6(376. 8/25) 1032. 0(92. 55/8) 1094. 3 (183.5/12) 2.73 2.68 -
40-60 87. 20'j1C70. 2(151. 5/6) 836. 6(104. 9/7) 849. 8(182. 6/61 , 3. 25 (2.27) -
b0-75 " iI1251.3 (208.0/9)
1 1121.9(1T6.7/14; 96 7. 1(160.5/11) - 3.45 -
75-90
> 9C 1569.4 (456.4/22)
" 1632
2
6
/ 1219.2 (431. 1 /6)
12 1253. 8 (388.6/16)
87
6/ . (2.14)
3
26 -
:
26
(4
0. 9
.
30) )
1451.8 (376.9/ 10
.9 (252.
7) ; - . (
..
)
..
4
CTR ~N 042447
