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Council for Tobacco Research

1984 Report of the Council for Tobacco Research - U.S.A., Inc. [St]

Date: 1984
Length: 75 pages
CTRMN012459-CTRMN012533
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25 Sep 1995
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Ctrmn00010849-2859

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Hobbs, W.D., Ctr
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118
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ANNUAL REPORT
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006
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vvr30a00

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Page 1: vvr30a00
ANDREWS OrFICE PRODUCTS CAPITOL HEIGHTS. MD (K)
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. Organization and Policy The Council for Tnb.cco Re.earch-U.S.A., Inc. is the sponsorinR al;ency of a pm6ram of research into questinns of tobacco tase and heslth. It ia the uutRrc wth uf an orRanuatinn fnrmed early in 1951 by tobacco tnanufacturerx. growen anJ waehnu.e- mcn Researrh support hn been mainly thm.Rh a pnsEram of Rrams in aiJ .upde• memed by contracts frx rescrch with instnulions rd lahiwatories, ilK ('aim J Jiscs nrn oMurate any research facility Tla Sctend6c Advisory &+rd lo The Council moeb r+c6ularly toevaluale aMdica- tinns fur research suppott. judging them solely on the basis of scientific merit and rek vance The Council awards rtserch Erants to independent scientists who ane assured ctwepkte scientific fatrkwn in c.wsducung then studies Grantees aksne re rt cpm.fik fGw repnsinR nr publishing their findings in the accepted scientific manner-- IhriwRh mcJKal and screnhfic fannals anJ srneeties Wit t uM 1) flt»1es Chauman 1984 RF:P()RT r~f TIIM: ('OUN('ll. MOR TURACCO RMtiEAaK'll-U.S.A., Inc. THt: ('(lIIN('ll. FOR T(1BA(Y'() Rt1F:AR('ll-lI.S.A., IrN•. 90 Third Aveswe, New York. N.Y. 141022
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ti('1!':NTIFIC ADVIS()RY B()ARI) a111a• ('t•uncil far T..Lxu+ Rc.cuch - 11 S A.. Inc. a% ol rk.•clnhcr 11, 1984 I UON 0 )A('1)115ON, M I).• l'huirnrrn lmrJr/r Ilrxr•ma•rn 1'n./r...n.r/AioluRirul •frirn/r. (rmrnnrc) I•n./rttrN rr/ thr• l)rp.Irtmrnl..J Mrdi-tnr (rnlrrntutl Ilulvrraly Id ( haaKu (lntag.l, Illnww. kl('llAkl) 1 ISIN(:, M 1) I'lill:k M II)WI.IiY• M I). I.IMtr:dury ul I'alhldugy Natiun:d ('arK•cr Inailutc llclhcwl.l. MatyiallJ IIIiNRY I I.YN('II. M.1). /'r.r/r•itur nn.( ('hmrrn.ur I)l•I/JIIIIN•111 ul I'rcvcnllvc McJicinc anJ I'utdic Ilcalth l'r..(.• t~. n. q Alr.ln low l'rr~r.l. rn. Ilcrcd/tary ('arn•cr In.tilutc ('ICIFhInn 14nvcr.qy kfi.wd ul McJlcnlr ( )nl•dla, Nrlw.r.l,a 1)u.rr trrr .4 1 yrrrmrndd ('.ndr.r/nRv urwl S. trnn/6 /)rn•r(rqrmrnr Ilonthnr!t/wl Mclin•7I kcKdrt'h In\Illulc\• 1'a%alkn.l, ('ahllwnl. Vrvnnx A.v-. r.ur (•ahbwn/. In.lmltc 1/1 l echrwlh/gy, I'a.aJcna I'r. r/r t tnr s tfAl rr(i. rnr ( rnrrntn t) (i IIAkRY I'Il k('I:, M 1/. Anrrrl.un ('mr. rr .1.w'irh• ('rntrmriul Rr.tr.uo h 17.r/1•.un lblrvcr.rly ul ('uhw Nir/ llr:dth Scicncc. (•cntcr 1)cnvcr. CutlK:wWr lhuvcr.uy ul Glulhcrn ('rlrbwnla Sihlwd uf McJrcinc i C(/kIX/N II SAI()• ptt /). I.tv AItgl'IC%. ( :II/(.NnN R()SW1I I K N(1U1W1'I I..I'u I1 /'rn/rttur n/ (Iqr.rlrrxt I )u r•r tnr W. A111M )Iwlc% (•l•ll Sl•1l'nl•c Cl•nil'r I.:IAc I'I:k:/d• New Ynrk MtArJlc I .drw.d.Ky l..r ('.mlrr kc.rrull 51111IX)N ('. S()MMI:RS• M.1). , I IrUvCraly ..1 WLt.Nlan M.w1/Nw1, Wtml-ml/l 11k(IMM()N1)1I N(IWIWN• M 1) Sr rrntt/n 1)nrrl.rr• 'llk ClMUlcil fnr Tuh;oca'// kc.rar.h I/ S A . lur ('lhrm rd /'rr./rlaw aJ /'adneh.Xv ('ullcgc uf 1'hy.K•ian. & Sutgcun% uf ('ulumhi•r l)ulvc/.ily Ncw YINk • Ncw Yllrk 1'r.•/rt t.a .Ind 1 /r.kl I A•partnknl ul /'.lttwd./gy 1 t/nvcraly uf Manu/lha IIcalth ScK•ncc% Ccntcr W Inn/rcK. ( :maJa MI(•IU11.I. 1 BRI:NNAN, M 1). 1'rrudrnt un(( Afr.li.•rd /)irr•1 low Mkhlgan ('anrcr huurntalilal Iklnli/, Mwhigan 1OSI:IMI I). P1:I.UMAN. M.D. Mrmhr•r (rnu•rrtuv). Rcscarch Imutulc 1+f ScriM+. ('Imic S. riMt. ('llnit and Rctcarch htwrwlaunl 1.:/ h/ll.l• ('yldurnia l:.ln.w. ),MUn:,1 nr 1lnnwrM.lr/ity San I/Kgu, ('alihlrnia WII.1 1AM 11 (;nkl)Nl?R• 1't1 1) I'r../rttw .4 Arrd.wnv (rm.-rlru.) 1'..1t I lnrar.NV *.Iw.A .d Mc'.ht low Nrw I l.vrn 1.wln.v h. ul tickallflc ti1.IT of '1'he Cnuecil SIII:LIK)N (' ti(1MMIikS, M 1). S.irnlifd/)nrr tr.r IX)NA1.1)11 VOkl), Ih1 O. IUARMON C. M/t•A1.1.1`1'1•k, iw , I'n I) A tt.N uur Kr.rarrh I)irrrrin A...rn rut.• Artrurl h I)rr.•, tur VIN('1•NT F 1.ISAN'1'1• 1) M 1). 1)/1V11) S1Y/Nh• Pit 1) Atvw lutr Nrtrurt h l)errr low A...w iutr Rrtr.ul h/)rr.•. t..r
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C()N'f M:NTS 1ntr4.liN uun ( •hnnnl I~:% Iv/.ulc #.l M/cc h. (•Irarctl. Smld,e. . . AL.ILN t. 1.1 I(clwNt• . .. . ('.un cr Kcl.nrd SIM1w•.. IIN• HryNr.lliwy Sy.h•nl 5 7 IS It tK Ih'.1rt afM1 ( n1111.1tNM (r) Nrunhdl.anl:K ibk.gy .IM11'11y.i1d..Ky I91.un1.NUh,/•y aM) Iln.lw•nu.lly InunuMdi,l•y :uKl AJ.qM1vr MI•k h.uu.m. It2 Nh 97 Mrtal..-hl Stu.hr. 117 I pNkn1iu61Fy I_'ll I?1 Al11vc Pa-p•.1• ('IN1qd1•IrJ I'rup•11. . , . I1t 147 IMkR 1/1 tiCnil>t AuUM),. . 1d') IMk•. 1•1 Itirn'Ipal Invc%t/ra1oK%. . I lntroclucddon In 1I/NJ IIN• ('4N/M iI puh//.heJ Ihr IiM1inK% ot a nlnc year .tuJy in which mw r wl•Ir rtlNwwJ u* clyalcllr .uN/kr inhalatkm. I IN• rr.IJt. /Miu%kJ Ihr.r' MMIr ld IIK .nMll r c.plvJ aniMal. Jrvrhhw J INdnNI n.lry 4111.I/INN1~ 1 CII ~ iN IMNIIa, nrK•r I+rtlrc+rtrJ wnh a parr d arl iMbrcn JiJ /Na krvc .II:n/1N.//11Iy IIN IIV%CJ IU/II! \'aM'e/1 ahCr prllkwll,y'J -./IN1{d• CAIMNuH'. a1NI IIN• IWCriII uumhrt. 1d INIbMNlary M•lyda.nls iJrnlllw•J werr MN .ratlvlically siymlirautly Jdlcr r IN in the .nNll,r l•111NhCJ MN.'C. cIM111kplYl Ml the %haT %nMIkC•cR(NewII /N .tK 1(c/Nlusd nIKC A.ulnncny ot the .tuJy aM+rars in this rrpNt Aginning un page 7. 11 i. taken verh:uim /nNn thr h.st, ".l7mmlr I:a1Nl.we rll Mw•r lo ('ll;arettc SIM/Ar." whK h 1, the lulal rcpl.rt nl x'n•ntia% at Micnihiuk/gical A.r.aialr.. hK•.. an iMkpclNk•M re scarch clNnpany in (klhrxla• MI). The wnrk was rklnc there nMkr a cINN1a.1 with the ('mIM J, which haJ Ure hlNdt pnnlcd. In a/4wcwnrJ tu the hlrlk, (k. Shckkln C. Srlmurct.. the ('ouncil's Srlcntilw• 111rrchu. wnnc• "The e><prnnlents repre.rnleJ a JetcrluinrJ rllort tu Jrvellq+ r.ua ahk •rnlmal nrNkl inwJvmR chtrlnic ciRareue srMoAe cxphurr nl InhreJ nwwu straln% kMown lo Jcvr kq+ varilws hi.hqnlhllhqcir types ut IunK carciM.ma a/lrr Inlratrachr al uhnim.trdkm ul pure chemiral can•iMrgrns. 11 is helievcJ the rcpwt will tK.oI lntcrra hr OM/.e engaged in inhalalinn researcA and in the Iie1J ut investigating hunran snw4,/nR and health rrlatHNl.hq..." 'Ihi" rrpM clwNains abstracts n( 174 Iwpers that have appeared in the scleMllic nlcdia with a.#MlwkJl;rmrnl yd ('Iwncil .ul+lllwt The IiKurr MInK. In at ka.t 2,S?S llw• nnnlhrr of .cirntilic papcr% arkM.wkJFinK sw'h suMrwt puhh.hrJ .IM•r the ('twn cd began .upwNtmg rr.rarch inlo ur.IkinF aMl health by iMkrrMk nt .a M•nn.1. Ac ol lhr r/MI n1 1/1114 • the ('aam•rt's pnlptarn haJ I+IUvirkJ /MNr Ihan 1 al • S(M 1/11M1 a/ S2th invcaigahK. 11K 897 rIrlFlnal pn)lecls in 295 t1M'JN'aI v'hoNd\, hlr.pltal% aMl rcvarch insllttnNlnc. S
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Chronic Exposure of Mice to Cigarette Smoke F•.rll..M•rnK it /hr srrnnwrrr irr -inn /rrwr the h.r#A. "( •hrarrn h yNlturr .o Afr. r in ('rx.nrnr Sm..1 r." f6ur r rMrqrritrt Ihr Jrrwrl rr/nr-f n/ Afit mhnduKr..a A t an aUrt. Inr I be are rn.n turnmmr:r•t /rndrnxt f-rnr the 197S /vY 1lnulrr f.hnrnA M he. Is nm.,r, rh,nr /r) lMN1 rnr..• rn4ulrJ the rmdr/n.m urrr X11f100 r tKerrers 1. IN'rR( ll lll('ll(1N I hm 1% Ihr I mal RcIMMt hn ('iwur:M•I IMI111 crlbtkd• "('ig:ucnr Snwdkc Inh.ll.luun %111aIM% 111 MMt• " I IIN It•14N1 tlC%t•f11K\. II the I.M IIIIM'\ and CtIt111M1w'nl, 2111M• rcwll.. IHNII IhIrC Ill./l.w %nwdc Inlr.d:uMUl NuJav• and 11 UM• rr%ldh 114N10 rt.rolLuy tludlrt 111.11 NIIMMNIt•II IIM• Ihrh' /IL/IIN Iwll~,'rAIU% '1hC llvC thdlwcr% rhdl InAkC ul. she 1'1/1d) RclwMl arr .unun.InicJ IM•rc 11. tA('ll.l'1•IVti ANII t:()(111•MM:NT 17k ciyarcnc anwd,e IeerlcrAlitrr aal aninul httklinr. t•trnlutM•nl wt•rc Ik•.IrrM•tl in pruvMh• hiyh cyMhurc lit Irc.h nwimlrcanl cigarcllr %IIM/hC IM1 d tl,tdy h.111% ItN A IIIAMK (MM11tM11/I she IdcluuM• td 11K An1114k the I:KIIIIICI, (MUVMh•tI 11M• lulluwrnr • I wu SIrMd,C I:RplNuft' Mxhint% 1Sl{M 11 It arwl ('-, tMM• %11.1111 rqrlwrr nu chUM7. Ihrre an/ntAl ftlnliinnlCrll tIM1s, (wt'111y-I4110 CRIMhUrt• 11MNIUIr\, AIMI •IIN) anunAl 1 c%Ifn1111 Ir Ay%. •('al+atily In c111MNC 4110 mire .Irm/Naruvtu.ly. and up lit HNMI nnac IM•r tley. nl ril!Art•Ih vlrMlke under cnlwlNinnv whtYe ktcalcf than tMl'.1 td the ww1Ac (.:nutu lalev werc tkphilttil in the reyMrAhry Irawlld Ilii nlac • IIIKIMIM'n1a1MM all the tI1qINNy n( NIMIkC IUCw•MCtI Nt IIN Illitl• tluflnl; cxh t•NIIIhUfC k'\tMMI. • tiAll'ly \y%Il•111\ IIIA1 &%WItYI eR111hU1v all nlKe In %IIMtIIC only unikf IwCNI t'RIIIhUrt• t•ttIMhIMNIs. •(u'IICf:11NM all t'1p7BCIle %Inllkl' WMIIY CtMMINMNn p1Mf1/IIt'lI IIM tll':IN•IIC (Y1M, mnM0.e iwnrV/l c4MM'CMrA1Mln and %nMll,e IlartKk %itl •(':Ir:Klly (U IMNNC 111t IA NI•IMMI Illlfc as a It1t1C UtMkl l4lrMhIMM1\ that m.Mrcd a ckan nnd clMwu.IkJ Cnvintnnknl, 111. ('TR-100 (1-NNI. ('(1-CAR('IN(M:t:NtSlti ANII ('IIR(1N1(' INIIAI.Al•1<1N OF 2A1('1(:ARt:T1•!': SM/lKt: Tlw hnl nthaL+IMm autly Wilircd Kernurky Refercnt•c 2AI t Irarcuc .nw l,r Ihll-h IN htw nM twlnr ) at A th.-c ul -• I InR /ltllal p:MM'ldAc ut.INCr 171'M ) lr•f tlAy (R'/ IIM M14• IunK 1 hc estIt rlnM•d h.wl hMn marw nhh t Irvc%. 11 lo tklcalntnt• she rn/p,M 1.d dk fiI!arC11e wMlhe let•nerwllMletluiilnlenl an11 tlt•Itvrf y cytlelntMl lht• IC.1 Jnlutrl.llt( • 11 of ('um Iefnak mkel. 211a Iklermine Ihr 14611Wt1146fwal cllach ul dr1ly eap•.urc It. JAI wlMtle riRArellr ~nMd c m 1-l' 11 1/('wn flure uver a 12 - IS Inllnth ry rwMl, 11 at. hwx Ierve Ihe su~aclMlMhly tll N(' IF1/('urn ant) ('MI/An( ('um nut e ht lung t an. rr .dlrr IrealorcM wlth krMtwn t hemM al t'ara'irwrytcn.• ant111 w Iklemm~c 11M• t llt t I..d J.uly etlMhtlrc lit wlMlk cirAfrllc %nMe-r nn I mclhyl.hldandwrrlr IMC/111nJlwrtl lutur IunMN• A Itdil lll 14 /11 IItMC wt•IC ItUr INI Ir%l IIN 1IIN %IWIy 7 ~
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MNC wrrc Ib.rrvrJ.Iuring arNl InmN-.halrly allcr J,aly.nNlkr arNl .ILUn Irra1 IV. (°fR-101A. ('lIRONIC EXP(ri11Rt: (1F 8('lf'll('lIM MI('E'f(1 2K1 11N•nt I'11/ IIN• mnN.ka' r{tNNrtl J111111:11\, wh1la' :1 lYrtJln a11NN111I III :Nl.lplab.ln 1N1 urlCJ• ('I(:ARt: l'1't: ti111(1Kt: dN• d/ tIN• IN Un1:11. rN•vrt :N. \'IMrJ Ihr.nN.lC C\/N/vtir wl11NNn MNIN• al[IIdINN1 nl t .1.1c-r IIN•y ,IIM. INt./lNN1.1IIy Jl'lIN-mIt:11CJ vN/l. Ilrlti.w hrt•alhmg r ./F/!Ilu/! UI .N y:..laN9 'I hi. vllNNllnhalalian NuJy wa.lhr ht.l lk.iKrN•J lu ua• kNl Ierm /N "IAruNN•" Jorln/• c.IN..urr IIIIIIKII/:Itl'Iy alll'r l'IINMufI•, nlNr in 1IM VIN/11l• l'1I11N1'.t F/ N/IlV wrir g thuanc •11Nlke c.pnure. 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Ina'Nk'IN't• .lI II/Jh/•nJ1N I1111K III/INN% In ( I K I/NI (:111 alvt'..I•1r :NMYNN:III /INNIIJ..I wa\ II S'1 %tlN•ll' a•a1N.a•J .In1111.J, wrlr Ilh.rrva-J t./ h•Ivr IN1 nIJ11g91•nU lunl; thdnlYJ JUnag 1111 .nNly Ihr uNl•1 Irc'y1N•nt Ir.NN1 .dlvrvrJ 1/1 tIN' mnN.kl' t'RINIyJ 1!IINIIN Wa\ /NrlIN'lltrJ aI vr.d,11111,Mn.~111JF1••k\UIIIIIIJINNIII'AMnI Adrr211wark.n/r.INnurr•dwnNNklNe ul 1'AM/l w.l. 11M1'1 1wo INIw•r Ir.N.N% wa'rr a.arl•drJ wnh .uN.ke rt(NlaitC. NIu.U1N.U. uN•t.111L1~1.11.1 Illr IhNhl'J a1NI II1111/11~ D1 IM' MIN In•,NuN•nl.-I II('tI Ir(bn11n1\r wdh Ml'Arr.u1tr11111 h? Jll/crrnt cuNlhlna tN11/1 411 I1/11141,111N1I/1}Il' J1:IFIN/y~ in t1K IIItIr Alva'.JL}!t'nla' Il'aNN1\ w\'ll• l'I:1%\IINYI unu 4 aurf•NN•. rlvr.ll.lt Ilyprrldeaa 1AI11. a1vrl•Lu INNNINn(Nt'%llllg INNhIk. I AN/'N 1, .Jva..LN . nllqxa•..inF• INNlulr.l n('N 1, and .dvrular :NknlN .Irt IaNIw 1 A Al'/. ~.III:UIMN/\ la'~NNI~ Wl'fC \ IJ\~IIIrJ In11r 1 l•Itt•I'INIC• NII/:111NNN IIN'Ia1•Ia.le ISM 1, .yua nNNI% 1N'11111•1m111`N1• JMI NIII,n111Nh l\'ll lattIM1111J t1t'l 1 1hl' 1111N'1 aat\IINN11,/% 11NIINI IIN IINhYI INN N Iy JII Irfl•IIIIJta'J l'aft IIN11na% I I/I )l 1:I/NI a vaf M'Iy ill 1t11 tl'II l':/t111N1- Illa\ I 11C \:Ifl11NN11:1% a1NI l•venttl:llly t':111K11111e akti:llh./I IIN' :In1111aI I IN' INUgre..ive n,ltufc ul the.e Ic%Nm% wa.lMKunx•nlrJ alNl a ahcnlc d:pictlnp 1hr ev/du INN11/11h1'4 llull)'n•1111'1l•t wa% INhlYlalCll (%l•l• 1'IKUfe 29 atNl SCl'INIII Ill I)/ AtN'111ary .lwlle.wnhlllhcrktNlwncarunnrrn.atNlnthrr.tram.ulnllt'evuKFrvlrJ 11('111/Anl l bm a1N1 N(' 1110 'wn 11194 c wr/a' r11ctNN.J in Ihclt .u.cC ptlhilNy lu Ml'A i1NI11ca•J lung /ao.er.. 2/ a Iww• rr.pNl.r lo M('A alJuaeJ IIIOK tuuNN% wa% llhvrvcJ, a1N1 tl tlx t•atrlnl/l;rnlr aa av/ly hw lunK li..ur w/.lk IrnnlnrJ Iu 1~ grC:11r.111N M('A. IuihlwrJ by 7,x /ldlylltn 7.11 JlhyJrl..y hrnildary+yrrnc (Ital• 1,11 Jlotl, hl.th nl wlulh wrrc 111tN 11 11NNr :N l/vl' Ih.m hcnitdah/yfr/w t11a1'1 I/.Nly rlryrYtr la 2A1 tlr.rcnr mnN.kc JiJ nlq :Illrl the typr% ul Ml'A I/NI/NC1I IN/IttNN6Nyh'\NNI, LI/yrYl'tI11111t1..111•1II1/\h:/nICRINowJ/Ilnc Itw'rcwrrr.hpblvarla- INNI% It11M' IIN nla'/N C aNIJ JI]1111N11NN1 UI the kt\NN1%:1% J Iu/N11NN1/1I IhLL.111.N1 nI .nNlkc r.IN..urr Analy.i. u/ In1I1VN1U]I IYnI,' Ie%111fN .h11wrJ that lhc M('A •hanl e.INIVJ ynNq. h:Nl a hlKhrt lnt'iJrrlce anll//lr .INMCt lalcncy (ur all maliKnanllunK Iun111r% than thr Mf'A .IrN.lr e4 1111veJ Krlwp SftN/ke eaplr.eJ nlne lkvrMMuJ a.hghlly hlKhrr nN NIrIN r u1 AN1'N. A('N, a/NIrIN SN Ihan the .ham ctlNl.eJ /nw'e Mlalya, tll 111r lMwcb.pnN•nl ul .•ltlN•r Ihc.c 1•Iltrr IraNn% Vr n1aI1/,ylanl IC\NNI% wa. d.n IN'/l.ull/rJ 1>..J r r yN'•Yrr N. ' A 1 t IK arrttr .nn d l' I II J IM d aI1r1 I1N' /IN NICnI C alNl rnI JI%U /IN/INN1 U1 thc.r A11'A uNtul cJ (r.N.n. wIN•n cuolperrJ t11111r %II:1111 CIIN„fiI a'.Nllflll~ 1 I IN• n11111hr1 1.1 IIIN'l' IN11!Inally INII INl lr%l I/N the %Innkr, %h:1111 a/N/ \IN'II I:LNIIh w.1. !//s 1, 1/11•1.11N1444, rryla•ct/vl•ly Hnl' wa% flvrn mlr.n/.N ha•:dly Iu;NNNIN•r 1•nNlp u1 lnar 11N• nulnlt•r./l mia'c Ilul lln le.l I/N 11N' NaI' /.I/N/kc. 11/1' 1.ha/o. ~INI tl.J' t.Ilrl/ gf/Nlp% wr. 12//, ?tO, arN/ 1J11, rrylr/•uvrly. Ital' w:l. }:Ivrn thlrr tn1/r..N h/wrCAly Illll'rv:1k anll ~/INIkI•/~h:111/l'~INhYfI' wa-. NINGNrd INIr week altrf tlN• 1.rA I{:11' Iur:dnN•nl `IlNlke C1lINNtlfr t'tNNlnlll•1l1111 a daily h:h/% hN IIII wel•k\ Ihe 11114' IJ !K1 t It •Irc11r ./IN Ikr w:l% tklr r/11u1rJ lu he 11 2 /11r.11'M IfCr tlay IIl'r IINNIV• 11//11 IlN' /l•N1I1• Irlnu IIIe .nN//,e,.haol anll.hcl/ t•l/nlrlll Kn/1qr wlll hr rcpr.rntrJ 11r.1, lulluwrJ by dlr rr.ull. IrlNn t1k Hal' tncatrJ gr/Np.. lbr 111at1N l IInN'aI llrM In IIM NrNlkt• t1lIM/X'l/, lha/ll l•111NIVrlI, a1N1 lhl'II r.N111-.I nlla r wrrr +. /u11uw% I/') he nlaplr rra.an. hlt.k Nh ld Ihc mN r wl tr rNhl t I.NNbh..n. III•N /a1NhNllly Ir1lN/vl'J a111111aloo If/Nll (lle %IO/Iy 11 e. SnNIkC lN \hall\ l'>11NNIIIe rrlatrJ• INlhlrr rl'Iale1l, IN 11.N,"u/11CMC11 alf IM NINIke Ihlw (wllhkm./, IN lkvr/1qNnE Jlva.r. that bkrlr IeJ Iu Ihr Jra1h I/l lhr anmwl. ?1 K:IIe ol wrighl galn wa..luwrr in IIIr .halu a/Nl .nNlkr Fr/Nyr% clNlyurrJ 1/1 the .hc11 cINNa1/. 11 I)a/ly ('lHlh kvcl% avrlagrJ 17 2'% , I 4'I a1NI 1 1P.{ IUI Ihe %IIN/l.l', oohYIU afMl 4IC II FrlNllh, rl•%IMYYIvCIy A/INN11r tIK .ha•i/ cINNnJ., MM%• ol Ihr mice d/tvl ./l .uch nrlqda.IN lll.e:/.e% a. hr/11:d.11N/1a9N t':I/Krf~ I l VX I arNl 111wu.art'lNlu. I 11'%.1, whilr 411'% JICJ ul /NNI IN•111.I:LIw (l'.NNI. llph a% l/M1~.'CoINN111UICWINNna 1' II'!<1. na'11h11/1% ( -1'%1. a1Nl a varN•ly nl illt Ilknlal k.wN1.1 2('%•1 lllc.r vu/r lypr. ul k.illn. wa rr uhv IvrJ m dN .nNlka• alNl .hanl rRpl.lJ nlirc. 11¢1ai1rJ allalyv.lll the hdhlwlng Ir.NN14 wrra• /II,Nk• in .UNIkC arNl .halU CapNCJ aninlal.: 11 luno,' t.llll'Cr., 21 /NIn nMqdr.in: /f.INrat.Ny Ita1'I kt'\NN1\, I) IN11er nIN1-n1Y1111:I1IN- kL•\NNIh, 41 all IllaligllaMilY, S) IN'.NI a/NI IN'lk hMlM;nr/N11a., a1N1 6) IM•nWllllllne lil• lunNlr%. All /unF' l'anl'l'h IIhwlvl'J in IIK 11('NI/t'uul micr wrrr alvrul:U a1/l'INN-ara IINI /n:1% (AAl'/ No VIIIalIN1Y% l'eIl l'nIl'1111M11:h t1r tllhl't rU1/1NN6Ny l':Nl/1NM11.1~ wl•rC Ilha'FvrJ In 11w .aNlke, .hanl, lw alrll t•/NNt111 Ktnup. /1 Idal ul 14 AAl' wrrc Ilhvt vrJ /NI/ 11I a I/II:/I 111 4111 anin/:ll% at n.k in Ihe .nNlkc e1lpu.eJ Krlwp, whlle 7 AAI' wrrr /ll..etvcdlwlldt.Sl.hameRplt.eJaninlrl.Wri.k.1)alaan'rlya.l.a•rSrlt11N11V 11 Iln 1/Nn JlllrrclN wayo, /ININ':IICJ 111:11 rM/1hIIl'rl'11l't'\ werl• Id+.a•rvrJ hclwrrY IIN• .nN.kr .N .hanl rx/NNa•J Kruup. at p 4/1 IIS. 1 hc Inl'wkl IN'c l,/ A/1(' w:lv gra'alr/ nl dN' .nN.kc e*INVy'J rrlN/(h l/Nllh'JreJ I11 the %h:Mfl C*INNI'II 9I.NlIN (/1 ' 11 17I :IINI /IN' I•Ill'IN y.J t'RIMI'\%NN/ wa\ tk;etC:hCtt ln Ihe %nN1kC CN(nhl•J 1,'r/1111N lYMt111:If1'lI tI/1IN1 dum r alNlvd gr.Nqr+ ip = 1/ 1/1/ (kcunrm•e /d AN('N tr A('N war 1„lY7N LN \/lN/kr Ct/N1aYl ynNp1" aNI 21/t1S1 IIN Ihr %11am CIINII[VI F'hNllh 111 =• 4151 I/MNIa'IMr/. 11 11 IN ILtr11cy/1 Ihc .NCtulcINe 101 enlwr AA(' lIr A('N yirllkJ dlr IarKa-.1 dlllcu'INc hrt wra•n t11e .NN /k r a1Nl.ha/11 e r pt.rJ plNy+. 'fhr final /tw Nll-IN c ul A A( ' I N M'N wr. 44/V711 in IIN• vnN.ke r.IN..cJ Kt/Nlp clNnparrJ 11/ 2M/hS1 /a Ihr .h.1Y c.IN/.rJ'raup II 9
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I IN•.t ir$ Itlen t'% werr MN t)IlfRenl ((1 - 1) i'/I, but 1hl IunMlra a(1(ItarrJ I1NIrc llr/l'kly ul 11N• .nM11c ealrt.rJ Fnwp Ip = (I /M)1 A 1,.0 td live nt«I nt.rla.l/t tr.pnahny ttrxt kaiun% were analy/tJ I'AMA, uml•c.ll.nlI rhmnl., twuts ok•Jl.r. atlJ Iwul% r.lcrna. (1N[ uvrtall ult-IJerKr ol PAMA wa. 1!:< wh/ah 1• ttNlsnkrnhly h.wrr than that nhscrveJ in /hr Iwcvilws tlKarclte .nNAr.nNly llK nluulr'r td I'AMA./ntrcavJ w/lheaprlnr. INII tNrly rrathct! lV;. t1111111/; /IK 1.2,14 IIMNIIh%tll a'tr11/Nlre ( tNlf,'rtlNMl waa a rallN'r ltNt111MM k\IIN1 Ir11MM11 tIN• vlwdr and sh.lnl c.lrl..•d anunal. Ihr IK'eurretlce /d ttm~cVitNl was ~rratcr m thr .ham cslNnttl anolpl..ulnplttJ lu Ihr snrlke rtl+tneJ nlKr Ip =/11121 Iht• hnal uN nklN r r.l /hiunls was rr.l th/lerenl hrtwecn the amnke and •ham eyp!.cJ ICnwq+.lp 1/ ') 71, M/111N' k•snm tN tuneJ.l/KMIy nwwe ral+idly in Illr snw/kr t.plv d nw c/p !hl l lK• I.Ilrnk y fN•rnN/ hN tq11/s uw•Ju was slwlrter /n.nn,Ae c.prncJ nute p' 111/1/ a/wl .xuNJ/np tu arN• .naly.h, thr lin.d inritkncr u/ thl% k.Nln wa. Idwl hy/N•r /n \I/Mtkr l'a1111µ•11 amnul. /p 1/11/S/ The final inthkna•c uf twilia e.lrrna w;l% md /hlh'/r11/ hrtwet// 1IN' \11NAl' and .ham riIplxJ suwpt Ip - 111t/ Ilnwrvrr, IIN•re were /ntht ahtms 111,/1 Ihl. Ir•Nwt nat uncJ with a.hunt•r latenty in Ihe .nlllke e.pp/.rJ Klwlp ttNUp.urd ttr /hc .hanl rtphcJ Xruup Ip = 11 111). Ilw• tMlw'r mNl Irto{dJ.l/c k.nul tlhvrvcJ was rn•Ilhnl/s, an iMlamnlaltlry 1e.wN1 td 11r• h/dlw•ys Ihrrr wrre m/ Jlllcrrn.'e% hc/wcen the snNlke tnllrrscJ and .ham r.lN/a'tl FnN/p. A ttNnpJrr..m td Iht• tttuncrkt Itl all mallKnarlcit. dcmlNl.uatrJ a 27'(• Ini Ih'nll' ItM /IN' %IIM-kI't•al*mcJ anJ a:'1'1 /IMNh'nlr 14m the shalnt.I+t/.rJ amnlal. Ihe IINIIh'1Nr a1MI//N 1.ucnty wat rw11 thltcrcnl hrtwccn Ihe Iwu rnlups 1 hN• parlNular tyft• ol tunNU, h.v.l alNl ncak hlxusartuma, waa tds.crveJ Mlth a higher Ircy1N•/wy In dlc snrtkc t.INtvrl nntc amlparcJ tn t/lc .ham eRplncd mltr 7Ih'N tu/IMN% we/r h/rhly al,'rrta%lvt' 11fh1 nN'ta%l,hl/rJ /11 tl\~Ilr\ far renNlvell fr/N11 the I+Imlary ./tc A ttdal ut 2'/ hraJ arwl /w.k Ilhrtlsn.tNUas were nl..erved in Ihc .orJ,r r.lul.cdlnNC,tumparrJwnhxln/ht•h.lmctpt..•JKnlups Ih/.th/lcrrntrlshlgldy .ifndK.aul lp ' 11 1151 I a1.11surc 1u.nNlkc wa. J.aNl,qa•d with htNh ahlKher u1cNM•INc a1Nl •Iwwtrt latcnty td hcad and nctk hMu.uttNnas 111r nK•t hanlsm hy whlth tIN•sc Iu1lN/rs di vclt/llyd Is am kar. IIr/I1;1111(MtIrIN' (u11wMS /IKIWh'J Iyny+M/san•I/mas, rrlitulum cell aarttNna., and Iy/n1+Mtylar Is Iytnl.tMnJ kukcnliaa. lhe tNNal inriaknce Id tlw•sr Iunwwt wa. 11'1< in Ihe snrlkc cotp/.rJ arrl Iv';F in the .ham eapmed animals. l1.InK flwr Jlllercnl nx•th• INh Id analy.i., thr inrnklKe td thr.c tumllrv was greater. aml the latency periwrl wa. .INwtcr in Ihe .hanl exppKeJ rlMta+arcJ tu the stnake e><pnrd ;xtitnals (p ~ 111/S/, Analy.i% nl Ihr Nal' IttaleJ Ktllups wa% perGlrmed a. JesrriheJ alN/vt The i1M aknte of 1'AMA in Ihr ()al' t• snrdee e.plwcJ Rrwlp wa. 31'16. /y/r the aninula c*pnseJ 1// 2R1 u1w1Ae wlthtwl MaP IrralmcM, the int:idcna•r ul PAMA wa% kta than 21M3•. It wuuW .c'em that trealmeM with 11aP m1lJilit•J Ille macn111haMe re.pm,e n•.u11inK in higher rncNkna'e af the.e p/KnlenleJ cella in the lung 1)aily e.l>tr.ure trt 21( I tlgarr/te snNlkr Jurmg the lime Itat'-rndureJ lung lunww. JrvehKrJ JiJ ma alter Iht• Ina'uk'mr lu latcrwy in the Nal' 1 snwtke Rrlw(IS c/NnpaleJ In the Hal' / shaln e.prNtd KrtNq.. V, ('l R-10111. t'XP(ril1RE OF Rl'IF'l/('11M MICF TO 2R1 t'I(:ARM:TTt: SM(/KF: , 1 )u/nK 1971) lyxn, an eapn.urc ref•imen wa% tkvehq+rd tha/ rew/teJ in h.w /u.n Ily ItN la.l/l 2N1 atwl IAI uKurtlr nNtlc Ilw•.e eal.•.ure ttvrNhluNt% alLtweJ /ht• ..Ik'[lullnr, t.1 a lunl: 111011 .tlNly wFIrIrLy 11N• hntlu~ual ellet1./.1 .nwAe hum (Nllh tiKarrltr lypc% cuuhl hr .imuhannw.ly evaluatrJ Such a hlnl! tcr/o .tuJy rmphtyulr 1111\ \/IMtkt rRIS/Wrr rrFinKn wa% prlllr/styl, appruvrJ, atMl initiated Junng tik I'rxo ttNlu;Kl yrar In luly 1'11/11. Iw/wcver, it wa% tkcwkJ thal tht. .ludy .IM/u1J ma IN• ttNlq+IctcJ aMl Ihal \IMlkr Cx111hW1' WN/er IheK' newly Jr(In'J tINMI/1nNh wIN/Ll lt InmteJ tn Illr kn fth 1.1 tioK Jur/np whlch animal% ln CI R MIIA were lu hr c aIN.vJ lu snN.Ar '1 ht• rw flt•rtolcnts atNMluch•J in thr (') R-M111i were tkslyln•J Itl rvalualr t t naul .Iwat tcrnl luewt/Nrgltal rnJplNnl.lhal nuy ha• rckvanl lu Jrtrrtnininr Ihr IMdcnual hwlufaat ati/vlly ot wlwde rlrarrlte.uwd,e. 1 hr.uwrlr r.INnurr rcpinnrn hw in Ihr..ludy diJ /MN include «•sl prntKl% ha•Iwcro .//trr..fvr t/}ara'llc., u%rJ'an eot(fn]ure Iq'rMNI rlf It yy11nJ. per minuta'. a1Nl CtNnlnu tNl% rulNNutt' /tM 17 "lutla" 1n 1411 ntmull'S, lllit re/.'1/1Nn n.'Wlll'J in xll u4 I I'M Ih'IMh11e1/11rt Jay llrt /IMNNr Iunx, an awrral,'r (j)Ilhl/t I's ./YA•, a1MI 1!Il•ala'1 Ihall')Y< UN Llrn\r .11 1'AMA by IA wea•ks ul daily .ml/kr r.prsure. I IM' h/1hIw1111,' a%tay\ were %e1lY'Il'II 1'M the/r IMMa'nt1al /111M'eJlat tN 110411111401 hN1~.`- Irr/n rlIt•ct..d t lyarctlc ttlMll.e: II /nh/MlNlrl ql IIuI/Mlrtilry I)NA repair rn v/lra, '1 .naluLdMm n/ pulnrNlxy 1)NA %ynlhras In viUU: 3) IMMN'tMNt UI IN/I11NN1.11y a/vl hydurarhtm hyJ/u.yla.r IAI1111 acttvNy; 41 ImludilNr ul Innahua drearht..ylas,• 1()I)('/ artiv/ly. SI aurnlrnlalam /d Ihe I)NA datnaKmK efla•th ul p:utnol;n luny t'artirwvrns; f./ InJul'1NM1 t1( \Itta•r lhnwaJ1111 elathaMF'e (C(la in h.wn ularr..w, )1 allrralum /n rrrta/n Phy.iral rhararkri.nrs.wfi a% lung wrirM lwel :u1J Jry/, INNly wel~,'hl, a111I hM1t'I11'IIIN'aI characlrri.lir. %wfi a. I)NA, /Mlllr/n :MMI I/yJr11RY1N11111N• levt•1% in lH/np. R 1 a11cr,MMN1//1 Inmlune 1YN1111r/l'/M'l', anJ 91 altrr;N/1N1 /n rHlt' 011 atil'%/.t 11 r. INwylr toria/ly). (1s/ng Ihr Jlvllnnmrws cap.Wltr rrXimen as tk IinrJ in ('fR 14111. inluhltuN1.11 1)NA rcpalr capartty (r g. uncrhnWkJ 1)NA .ynlhe.i. I(IhS/) rwcurrrJ wnhln 11 wrrkl u/ Jady t•.p/.anc to 2Al llr IA1 a'i~arrltr atwlkr, Mrl was unrl lrarJ Iry a•alNl.ulr /u 2RI alrarrllr .nwll.r llw even up ta 52 wrl'k. U.inr IIN• raMdinutn/v a'Fn/N•n a% tk/i/w•J lut ('1 R M111/, nu 1/NA repair inhlhitnln wa. IJLrrvrJ 1.u r111N•r IAI tN :MI t/garlle .uwdcc even ahtt 52 warks o/ daily caprwre. Illu.. Ilk• rnhthlbtNl ol I INA repair 11 II )S 1 by cigarette .nMlkc wawkl.ernl tu hr tk prrw!cnl u1N/n clF:nrtlc tylN• u c 2A1, IAI ~• 2R11 anllhlr Ihc rapsurc rrKimrn (i.c. M/.cru/NL .nM.l.r pcr minntt '• IS - 211 ttytNMI% %IIM/l,l' per /IlnWle/. Rcplia'alivr ONA syMlt<mis (RI)S) in vilnr was slurwl:/1rd 2 lu 4 LJJ after 9 wrel. 111 r.pNUre l0 2A1 ur )AI cirarrlle snMde, but mM ;dtcr calawtr tu 'RI a'igarrtle.owlkc u.inp Ihc high th..e, lYMvenlNlnal t'R(111%utr rt'g911M91 RUS was.lunu Ia1rJ 1 hJJ in mire cRlNV+eJ NI eilhrr .R l llr IA1 rikarclk sawd c usm): Ihc . twunu tMla ei<1111aun' re I;i/Ih'n. 1)NA rr pla•~illn aa mcasart'J hy tritialcd Ihynlialinr inavwi.wa/i.Nl inlu lung at•11s in viv.u 1I:drclhnp InJt. (1.1/1, was inarericd 1• N/ A II/IJ in lung a1w11tachral us•Ins Inan 2R/ anJ lAt ciKarel/e sralke expl.eJ mia•s. Nt/ i1K'rea.r /n 1.1 wa.llh.rrvcJ m hl;whkr, r/lhln. Iivt•r, kiJnry, /K yAern Nviwknce wa% presraleJ lu.ugla•a Ihat dady r.pl.utr I.1 whok •nrd,r /rnhrr 2R1 ur IAI/. while %/iuw1a1/nr rNNnc/l I)NA rcph. a tltm, /nay InJut r un.a htvlukJ /)NA synlhc.is ut repast .yMhca% a. wrll ( Iady e.p/ .utr ttt 2R 11w IAI l/17arrlle tnNlke Ia/kJ IU au/;/lla'IN IIK I.I 111111pY91 hy she (NNt'11/ I1/Ur t'arc/a'I,~rn, NaI' 7,M-Jn./ 'I hus, hlNh t/K:urtle .uwlkc arMl \Y'nd1U t IM'1/1N11/ t aa /ott t,'en. Ir K Hal'-7.M Jitd/ were ral+ahla' nl stinedalmK UNA .yndK•./. /// IN/IIIMNI.I/y h%%ue, hut IheY r1ItYt% tlNl MII %lYnl hl IR a1lJ/l/ve, \yrKrl.'1\l/t. tN a1Na1;IM11%IN AI111 wa% lrnh/a'cJ in the IunK ahcr r a/+t..wr N/ 2Rt /w 3AJ a'/garcne srln-Ic u.u1F any c.(Nl.ure reg/mrn invralipaleJ. f'uhndnary AI111 at Qlvity was .unu/la/e./ 4 a. t (Idd after 1, t/, IN /I IIMNIth%ralA„ure Renal AI II I wa% //MIaM'r1I alll'1 tlally a'RINI%uIt• ItN 9 nlllnlha Ikpatu A/111 wa% unrllrtleJ al all tunr intcrval. II
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I'11IIIMM1ary, 1)1 K• atllvlly, a IlntenlMl nlatltrf II1111n1mIMilN1e wa% inJu.•cJ 2-luhl wilhm I hlrn. ,dtcr daily c.pnure tn 2K1 rN (AI .nMlke IlN 1.N 6 nwlnth.. Ltpn.urrlu?H1.N 1A1crgarrlh.nwd.rlaikJlacau.e.lnxk.trotMlhrerk.inthc 1)NA u/ Iwlnw.nary a'ell. Snr1Ac ra(.r.ure al..l /aJad to mllurmr Ilx• kvrl ul UNA J.unaFr a'au.rJ by Hal' lN llal' 1 1t-Jrul Sr.trr t hr1 ml.u ut r tl hanl:r 1 S( l•.1 w a. ialw rJ in INlne mart..w ce ll. n/ nucr :d tr r rtpp•.urc lu cnllrr :KI rN IAI .nwdic 'fhr uxlua'lem wa. - 2 IoIJ and wa% hr.t ah- vrvl•J.dlrr I wa•cA.uMl{,ecalwl.ure (•.Nninucderarylsure/nr4, 121N •thwra•k..lwlwcJ tw. ImdN•r nx rrav lo thr nurnlx•r ul S( •lic /nrrca.rs in S('F:. (x r.r.IrJ ahrf cr..an.Nl ul rtp..urr l.N at ka.l I wcek• whclhrt the mice wcre r.l.nrJ imu:dly 1.01 I werA ,N ah wa•r1. Ip • 114111 Ua1Nr.urr Itl culx•r 2111 rN \AI llKarrtlr .nwAe using the t•rwnuluuu% n•ylnr•n rr.ultrd rn an nx rra.r rn thr ccllularny /d pulrmNl.wy li..ue I)ody e.p..urc luen I wcek 1.1 t1 wl•rA% lalu.cJ a tume lt,•IN•niknl uxtea.e in IunK wrt wrtyht, Imlr Jry wcq~hl, luoy 1)NA •mll pnNr ln, anl) hrnK hylk.u~ylNlllrnc Ibr. rnt rrax• m ti.aM• rna.. wa~ IrAI'ly IIx' /l'~I/II nl Inl rl^:IKJaa'IIu1.N (NUItIr/atMM1 lbi. prublcralnln wa.lN.dl,rhly a hn•d rn,nldr.FatuN1 u/ the rnarca.rJ 1)NA .ynthr.r% rates ld+.rrveJ in Ihr.r amoul. (/a/ ly r. pn.utc a. 1111 and ) A I a rrarcttr .nwllc u.mK Jd Irfenl e tpr.urc rcFmk n. Ijdrd ta lhcr thr rmmunr .Ialu% ul H('(I li(•um mrre Imnwnc clNrynlrrx•c w.1% lklrnurnrd hy Irrnl• Id•.yur a.vy Nl'dhrt al ute rMN l hnNIM eRlNnure l7uvl•J IIt1n1=/M. ,t/1jN1'vvNN11//rll)xY 11( 111r('urnlN 11/11 Hia l•umrone K.Ha•. nl :du•ar I1 c nian.d Ln..d t )tl•. tnNn the nv,uy) werc al.o unrltt•tlrJ hy t hrurnt ctlr..mr I.. `K I 1N I A It qvrrltc .nr.f.e Wluk u hr, hrrn.urge.lyd rn the lurraturc th.d tlt•rc r. • rl-IJINMI'htf. tx'tw(y•n l//,'arctll• \nN.ll/ll/' and rarly 1NIV'1 ul nti'rw.l..lu.r U r whrn the nvarn-. •ur dt plrlrJ ..1 ..K yle.). .ra ylr Iuullly wa•. n.A uh.rrvcJ ln II(•11M um rnnc aIlrr %; wrr\•.d J.nly .nw.Ac ctp.wrr Vl. ('OR/11•LARY STltU1F1: P1IARMA(Y)KINI:1-1('S OF INIIA1.1:1) MA1'tal(IAI ti liIe IkIMN11NN1, t11%trIhulNN1, and a-kar:IMY wl.'re Ila•Il•rminrJ fi1r nNYMllll•. Hal', lh Nriaruntanc 11) I(• 1 and c ak•chld in ctgarettr .rmlke. 1)ata .hnweJ a•un.akrahM! Jrl - Irfl•nal•% anMNIF' (hr%r IINIr t•lawo, 1/I l ha•nlxal\ Nicntine, 11a1' anJ a•atnMd .M/wrJ r:11N11 fl•11/~If11x11/1Nt InNll the h/ng In INhI'r tl%\ua•% atxl.karam•c InNn the Irrly 'lhr I1.J1 btr hN rntrrnal rclcnlnln 11112/ wa% k.% dran IS minulc% hN niclwrnr. k.. than I Ipan hw H•J', anJ k•% than ?11 minutr% hw . atc.INd. 1) f( •.huwcJ little r.vh.trrhutnm IrIN11 Ihe 11111r, with a IIr2 lll pralef that ?4 h.Nlr\, The IkINNtInNI• IhN111h1/1nM atNl a h••nana-c ul % alca lu.l a..mKk chcmil al x•n...d wa../N/wn tl# hc Mkntn al l.• t atcrlBrl in crrarrnr .nlal r- i c the pharmacnAmclir. ld ea1c. h.d are twlt altered by the prrvrx'c r•l the ulhrr ahemKalt in ciKarelle .nwll e Grcatcr than'NrR nl Ihr rnhakJ t atra IMd, cu1N•r tn arKarcnc .nw.kc lN a• an arnrad, was lrwrwl a% a hcta glut'un.nala.r- lN aryl .ull•Na.c .en.ilwe clNquRa/r in the wrnr within twit hrwr. ul c><INnurc. lhe lkp.•.unNl. Jr.urhulirm• and t karancr wa% al.a Jelrrmined hN 12 11 tcb:rk a/N1ytpIMMIr.I I 1 n rt.rtr 1 I PAI a% a%rnplr alx•nlw'al acnwd I hc ph•urnaaadrnrtlct tul :N•to ...JvrJ 11'A wa, invr.IlKak d a% a IrNrmr.d INlNlwMCr in a Iwu Mal•r I/nIt1.1nIN1 AINI In..nM r..•ui . an ln.yr.. ... nr.l.1 .y.n'.n .h•, lbl Uw lunr L..uc Kc.u11. Inml twu t-.IMr.un nl. .h..w..1 d. d...rt f.%'1 .d Ilp• NUr.,ll 11'A .Il'/w.,nd/11 wa% LN1ruI 1l1 lhe rr.l n..~ n t n.. 1 I I'A ...1, r.q~ully . 1l .1rrJ Il`.nu IIN- IaoF via dx• hl.N1, with ulk tl•a.ull: axrunwlaln/n in ltlr hvrr, .LNnach• and inle.lirks up In IS huurs rHrr ctll.l.orc Hy dx IwNrr., ovrr )1MJi• ul the inhakJ TPA wa% Irwrxl in the fra-e% arnl 21Y% to the urnlc Arn.vnlvrJ 11'A uwlua'rJ a.pecilic hilx•hemical cva•nm in thc lunl;.. Ih.lt r., uwbl thun ld 1/1K•:wbvtly• widnn I h.N)r~ a(/lY /nhala1N/11 II'A Ihu.eRettrJ q. rllra/ nonwdr :drly anll wal lhcn rcnMwrJ Inml Ihe lung llw pharmacnl mrlil. Jata .uF Fc.lyd di.q xn..ohirJ 11'A may h:rvr rllccl. in Ule Ka.tainlr.Imal Irxl, in aJJrtnNr 1.. 11x• rr~INra1.Ny II:N'1. 'IM•.r Jala .u~1r1eJ Ihr u.e lrl 'l l'A m a Iwo-aagc nMNIrI I/N luny carainur-cnra. , 12 11
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Abstracts of Reports hrdhrwinR are ah.tract., aplanwed by the aullMrrc, rd reput% rM new rc%earch actmrwkJlerng .uppwt 1nNn The ('rwncd that have aPleanJ in .c rentilK rwmala .rme forrhlxalMm nf the W111 Rrl.nt. The name rA the Krant recipient i% in it.hc.. The aMtra.t% ate KnNyx.t unJer these hcaJinR.: 1. ('arxer NrlateJ Sludic., 11 lhe Rr.l.rratnry Sy%tcm, III Ikan and ('inrolaliwro, IV. NeunKthatn.acnh.gy anJ 1'hy.e.hry,y. V. 1'harm:.rdr.Ky and Iliwkhemi.uy, Vt. Imnwmrlr.py am/ AJalwrvc hh.ham.m.• VII MetahiJK GuJie., Vlll. IipJcmMJ.hty. 1. Cancer-Related Studies III(711 t1I N\ITY I.IW IPHI)11:INS IN.( RF:AtiI: H11111 HINI)ING (1F A I9)I.YNtI('I I:Ak ARUMAI l(' IIYI)N(K•AR1I/)N ('AN(•IN((:1•.N T(11)NA ANI) (•AN(•1N()1:1:N INf11A'1'1:11CY:1.1. TRANS1iM(MAfH)N AJNat+tive emMK•yur.i% rrlliprnNein.ll.Pt..pcrifie.l by (.1' alwyxrNCin homhng In rerrlMoN% rm 11K .e11 rnemhranc rna1eJ pil r.gir»ls, i, pn.pr.ed a% a nMdrani.m /rN inlern•rhialNm rd 1.1' hawnJ (ipophihc cnnq.wnJr inln cclh. ') ran.l.wt rd Irryy+lnhc IYNn(MNnNI%..u. h ac hcnio 101 pyrcne 1 HaP/. iu reputcJ tu trc a/una awr ul .erunn I 1' rn .yrvr, and la reprewnt a pMCMlaI n>echanisrn 1rN n.wemcM .d tfaP /tunr Ihe tweKl.d n/ enlry .ne Nr.whrr tl..ue.. In the pre.enre rr/ high rkn.Ny IilerqnrNein., a nurlagcnra Hal' nr<Ia1ndote wa.luwnJ InteOular ONA at rkyreneJ kve/% when crNnpareJ lu.rllt e!.Irr+rJ lu tIK umlrpen in the abxrk•e rd high Jen.ily Irprlrrolcinc 1•etal call w•rum with hrw kvel% rd IiprionMeina, yoeciNeally hiRh-rkn.Ny IrpqnMa•rn., i, a.wri.ICJ W Ith CI IKMM ItKlhyh-hulaMhrene-InN/a1N11ranYlnh11a1NM10l C.111114) I'l/ ! cell•. whrk a all v rnnr with a.igndiraM rrar nMrslpul rA hiRh-Jemily Iqwsi.nwein% rryuuc% up lu a yNMx nKrca.e in nK•I1ryklw+taMhrene c.rrrccnlr:Ninn Iu achreve.imdar kvel..,l tran.• hMm NMNr in thik nrw.c emhryn cell line. When crnw-enlraleJ serum hprnwem. 4N purlky! /11)1. wcre added h+ Irlal call xram a.rnlaininK MCA at Ipgiml, the (• tllr II/I H! tranJrKncni.m In•yuency waa .ka•rea.eJ n+nqvareJ 1u Ihe tran.larmalnm Irr- yurrr•y achieved in Ihe prr.cnce al /µK/ml rrf M('A in 7eta/ call xrum w11IMM/1 .ulqrknwntalNU1. Thc.e rewh. wK}.e./ that hiKh-Jcn.ily lipqxrotem panitamrnK @o1 LIrTlnlir pdynurkx anMrulrc hyJnw•arMm muaKen% lnwn Ihe cell .ulture nM•rhuin nuy e/lavlivrty re.hK•e Ihc crnK•enualinn.d carcirMVen available /rN mlerartnwr wnh cellul:u 1)NA in r•itru, whirh. in turn. IIYy he a\NK/aleJ with rktrl'iwJ (aN 11M-r4•/1 InJIM'eJ tran\IrKn41tNN1 nl cells. Hu\IKr, r). r.L and HenrJict. W. F. MuhHiun Refrnn h 111. J?9-I1V, 1411). ~ (Mlier.rppert: Arnerican Carxer Suciety and Naliunal (ndilwea 4911 kalth 14461" thr (ienelic. ('enler, 1)erartmenl of Hwrh.gK•al Sck•m'e.. Nralh 'Icxr. Star Ilntver•ny ItenNrnI anJ the I)ivi.ian rd /kmaurlr.Ry-l)nrrrlrpty, 1ar. AnRrlr. ('hil Ja•n'. 114..prlal, aml I)epartn.eM rd 1'eJrauw., 1lntver.ny .d Srwlhrrn ('.d0l.wnia S.•lwwd rw Medw•inr, I.r. Anlteles. IIIIMAN I.YMPIIIK•Y71.1 TRI:AT1:1) WITII r 7. /-/I- INIIYIN((/XY r-1.111 1:1`l1XY-7,N V•lo I:Ir)XY 1.M!1,I1/•11:1RA11Y1)Nl)HI:N%(lf../I'YRI NI KI•(rI1K1; I(1W Irl•.N\IIY 111'1/1'It1111:IN1111R I)NA I:X('ISI/IN W PMR In the pre.enl in rrn.. .IoJk.. huroan IyorpMrcyte% which were monnnlorrn rt
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.h,n1,I.,Ir.1 .Illd lkpktr11,r1 htN>f+n,lr/na, wrre founJ tu tw Iklicirnl In ItNA rRU,nNI rtp.ul tvlNt.rlIy rr11ua1cJ in tfN•%c tcllk in tr.plNl.c lo ItralnlrrN wNh a dur.l at11nK L.IynIN k:u ,N.Ntl.rlla I1ylIr1ltarIMN1 t'Jn InI.I,Yn I ympMr yl.•. r/t/lrt Jrpk'h•d 1,1 Iqr. IN..Ii 111~ IN VII,1,1.•uw•mrd w11h hunun II.w llrn.dy IIp1.pu,Irln.l/Nnlr.1 I)NA t aanw/1•lIt ,Nklua 1. w1N. h wrtr IN,1 ahr/N1c11PF'r:ll+hl. •rlly llt./(III;N,•hahk 'l hr .LdC t11 III111- (,/.N. tn 11f pls h.,n dIJ IN,1 •altrr Iy1nldNr ylr uplakc nl IhynnJlnr Irnnn IIN• nN•J/unl I ymIANN y1c, what h w.•rr ak•I,k•tcd.,l 11pqNaAr/n., Ift•all'II Wllht'artlrN,F'r/l• :In1I N/hw- yurntly .u1q•MnK nlrJ wlth k/w Jt•n.lly Iq1lqNlMrin.. rcl'.nIN•J /llr ablhly 1.s rnFaf•a• lul IrNA rta,.NNI rcl.eu "Iha• Ilala .uFgta that rilher hIw ak•ovty hINyN.NCln/.lo tN a a.•nq,1,IN•Nn.l .•1 luw Ja•n.,ly Ii1r,INaMrinl.l, iv rrquurd hy hurnrrl lynq.h.Nylr. in ,N.A•r 11, nnll.dr.•aa1.NNl /epan aul tarcilw.Kcn danuKcd 1)NA l.t. 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