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Pin\ertrxr, 11 . Bhaeae. D. Rana, M. W. and FFoltwict, S ('an.rr Rrrrarrh )1 14tl)-14e7, 1971. (ItArr awppurt: National Instrwte of Mental Health. From the 1)epartmcnt of PhysiobRy. S( l.ouis University School of MeJrcrne. Sr. I oun. ANTITUMOR A(-IIVITY OF ANTISERUM NERVE GROWFII FA('IOR (AN1I NGF) In an ttcmpt to determine svActher anlinerve growth factor tanti-NGF) aftecls the growth of chemically inductd twnors, newborn ('F-1 mice were in- jcclcd unccuunecws)y with "Wtlkonm" anti-NGF for the flrst Ave days of life in increurnR dr.ses ('ontrol mioe teteived .w equivalent volume of hrxse serum. On day 27, all ammals were injecKd subcWaneously with 3 mg of brnio(a)- pyrene Three days Lter, hs1F of the rnioe which had rectived hrxse serum were given three rnfcctrons of wkotine daAy. Results irxficatcd that pretrca/mcel of nimals with anti NGF delayed the appearance of lumws induced by hervo(o/pyrene While in the control mice, tumors began to appeat frorn day 27 of the fir,t infcctron of bcn:o/a)pyrene, their appearance occurred only at day 90 in immunosympathcclomartd mrce. LiLewise, nicotine prelreatmcnt also dclaycd the appearance of tumor until day 100. Both these tretlmenu, i e., anli- N(iF and nicrainc, not only delayed the appearance of lumon but also caused lower incidence of wmcxs Whrk nicotine treatment delayed the first appear- ance of tunror and reJuccd the percentage of incidence of hurrxs, it caused significant increase in the averatc wetghl of a tumor. Bhocor, d, and Rana, M W Proceedings of thc S(crcly for I rprnmcntal Biology .rr) Medicine 11NI1198)- 9144, 1971 Othrr .rpport: Natu+nal Institute of Menial llrAlrh From the Ikpartmcnl of PhysKduzy. Sr I ouis (Intvcrsily khool uf McJrcine, St. I .ouis. CHFMICAF. ('ARC'IN(X;ENFSIS IN SYRIAN F(AMSTERS This is an eatensrve review of the papers on chemical carcinoscncsis in Syrian hamsucrs (!<lrrorricrrur •urarvt aY/0/Yr) which have been puhhshed since 1966, when the tasl comprehensive nne on thc subjccl appeared For the purptne of his JiuussKxt, the author divnks Ihe various papers Inlu sevcral groups classif-icd according to the systerna involved in addition to two other categorres, check pouch lumon anJ immunology of chemically inJuccJ neo- plasms In the seclNNl entdkd "Genctics as a Mr>,)rlymg Factor in ( hemical C'arcrmrllcnesis in Syrian 1lamstcrs," the author Iw describes some hitherto unpublished material of his own demonshadnt that genctK Iacwrs determine the rc.ponse ol hamslcn to subcutanccws inrcclwins of 9, 111 Jnuclhyl I, 2 henranrhraccnc (1)MIIA) (Canccr Rcs )2 1M) IM., 1972) Ile cuncludrs that nncc, in hn opinmrn, ncw significant rok of gcIKIK f,..tur• in ccrt.m types (if chcnoocal carcinnKrrxvs in Syrian hanrsten has been clearly Jcmun•lratcJ, it is inywntant tt uw int.rc.l linrs ur their hyhrids in such wor\. I Homburger, F. (Rio-Rrrrmrh Consrfmnrs, Inc ) In /(omburRer F. (ed ): Putholoyy r./ the Syrian Nar.urrr. Pruerru in Espr6 mrnruf l rnror Rnrarch, Vol. 16, Basel: S. Karger, 1972, pp 152-173. Other sppport: U S Public Health Service, Virginia and 1). K I.ud.iiq Fcwndatiun, Fannie F. Rtppcl Found.tion, and American Medical Association -Fducatron and Research FounJaticxr. From the Bio-Rese.rch Instilute, CsmbrKlge, Mass. IIIE UFAF DF.X 1 RAN.POLYRIBOINOSINATE-POI.YRIB(x'YTIDYLATE ('OMPLEX: PFIYSICAL PROPER711S AND INIERFERON INDUCTION To be abk to delineate the mechanism of interferon enhancement, uudles were made of the pbysKochemKa) and biological properties of the rI•rC-DPAE deslran complex. E.periments were carried out on human neonatal cells and mqu+e I. celk which were grown as monc>tayers in MFM containing 15% (v/v) (clal calf serum and incubated at 77° in a S'X ('O. uncnphere. Bovrnc vesicular stomalan virus 1 VSV) was harvested from VSV-in(eclcd mouse embryo cells. To assay for interferon induction, cells were eaposed to rl•r('.DI:AE destr.n complexes in solution A for one hour at 2' or )7'; then the cells were washed and incubated in fresh medium fo. If/ hours. A series of tests waa then run. In summary, the results of these eaperin.enu suggest that DEAE desuaa potentiates interferon production by delivering more of the rI•r(' compks to Ihe triggering site. It does so by increasing the uptake of rl•r('. through the aggreRalion eflecl, and by renderinR it ksa susceptible to endonuckascs. Pitha, P. M. and C.rrrr, r'. A. Virolory 45(l).777-7t1, 1971, O/At'r aupportr American Cancer Socie/y, Maryland Division. From the Deparlmenls of Medicine and Microbiology, lhe Johns Ilopkins University School of Mcdreme, Bdtimwe. SIRFPTOVARICINS INHIBIT FOCUS FORMATION BY MSV (MI.V) COMPt.EX In an attempt to sludy DNA polymerase inMhition, the eAects of urcpw- varicins were tcsteJ on the efliciency of Iransformatarn by Mokrney munne sarcoma leukaemia complex (MSV) in virro. Also checked were the abihtia of the streplovaricm compks. aa well as Ihc purdl,eJ sueplovartcins (A and Dl. su abort trarnformatinn of B+Ib/ 3111 cells by MSV. I or these studies, cells were grown in thc presence of incrcasinR conccntratans o( antibiotic until cell growth ratcs were rrb+trvcJ to slow lhose s(reptovaricins (complcs and I)), which are acuve inhibitors rr( the MI V 1)NA polymcrase in ccll free mr.lures, hLKkcJ the formation of MSV-rnJuccJ loci 1 concentrations which Jwt nd impau thc Jrvri,ion rate of rwrmal cells In thc caae of cornplcs and O, focus (urmaNK.n was bl.akcJ at conccn/ratrxn of anthhwrlic aM.ul fuur told kta than that which J.•crcax ccll growth In cuntrast, the stnnunally related rnacrohdc A, whtch IjcLs inhrbnory adMM on the vual enrymc(s). was ina.tive in Unuc culturc Ihcsr results suggest that Il.c cllccts on hhr k.Jc of tran./urmatwrn art Jue to a selective inhibition of RNA .Icpcndenl 1)NA Irdymcra.c hcuusc inhttN 16 17

lion of fucus formation parallels the inhibition observed in the enzyme assay. To lest whether ternporal relatwnshrps eust between virus between virus specific protein synlhesis and viral ONA polymeraae functrors, the native dmreric form of the virus induced interferon protem was added to Balb/ ) f) cells rt different bme intervah. before and during infection. Results here inJrcale tt at the re- Quuemcnt for vuns specdic protein synthesis occun within the first 24 hours, as does the function of the "reverx trarncripuse.` Also, it was seen that the antiviral effects of streplovaricin U and interferon were adddive, wurstinR that enhanced rnhrMtron of focus formaliow taw be achieved by simuttaneous block- ade of transcription and translatio.. C'erter, W. A., Brockman, W. W- sud brde., E. C. Nerrrr New eiolory 2)2:2t2-211, 1971. O(Atr .upprt: American Cancer Sociery, Maryland Division. From the Fkpar,menls of Medreina awd Microbiok>lly. The lohnu /lopkina Univenity School of Medrerne, Baltlwtort. SLA E(`TtVE INIIIBITION BY STREF?OVARICIN OF SPLENOMF(3ALY INUUCFF) BY RAl1SC11ER LEUKAEMIA VIRUS• This paper reports the effect of urepsovaricin cornpks on Rauscher Icukaemra nrua (RLV) infection of mice. ln Ihese anrmals, RI.V induces iniually .n erythrnAlastic proLferatpn which results in splenic enlargement. A change in the cfhciency of virus induced cellular proliferation is reflectcd in a dccreau in spleen werghl, whrch thus strvn as a quantitative parameter of chemotherapeulrc eRccl flmnfected animals grven streplovarrcm complc for IS days had no change in spleen weight RI V rnlectr.n resulted in a three to four fold rncrenunt in spkcn weight by day I S In contrasl, streptovaricin treated mice, fed drug Irom 24 hours before infection until sunfsce, had smalkr apleens throughout the period of observation Chcnxuherapy resulted in about a two-fold reductas in spleen weight. Borden, E. C., Brockman, W. W. arsd Crtrr, W. A. Nature New Siofory 2)2:211-216, 1971. O(Aer .rrporl: American Cancer Society, Maryland Divisicsn. From the Ikparsmesu of Medicine and illicrobio{ogy. The Johns Flopkins University School of Medicine, Baltimore. •P.MWJ r: sd..u.. trrww N fbyw..kr. 1 3ri_.~q.lr t.aer..d ~....ae. t.v.v.J. .r vr.. ANTIVIRAI. A(-IIVITY PRO[)l1CED BY TFIE POLY('Ylll)Yll(' ACIU IiEXA1NOSINATE SYSTEM Mrnt studree indicate that only the double stranded homnpnlymcr pair of p.>tynosinrc and polycytidylic acid Ipoly IC) can ir.Jucc interferon. h,rl in a few cell Irncs, ungle stranded polynuckotxlcs, poly I or poly (', can serve as rn- duccrs when they are applied at high concentration or in the presence of la•lytr..r. .rtnq.rurwls Rc.cnlly. it has Leen nhscrvcJ that succcssuvc adrnrnrstra- 1•.•n .d rfw r••rr.~l••.wlrnI h.wrrrlydynrrr. r.n cyu.l r./ snrhal thc anlrvuat .. ".rr. ••1 rhr 1.•1, 1( ...nt.4. I l.cse p. l,.ul.r .,uJres n 1gcsl. ainant ulhcr prnsubdrlics, that th: compkmentary polynuckotKles may form a compks /n vivo, nr that the two strands might functwn independently within the cell In an effort to further clarify the role of secondary structure in order to ursder- stand the mechanism of rnductinn by both polynuckotides and natural viral RNA, the authors tested a compka formed between high molecular weight poly C, and low molecular weight oliro I. While this cornpka has the ume chemical comprnition s poly 1(', the slabrhty of rts douAk heh drRera, so U,at tlv: secondary structure can easily be manipultted. leaving the primary slructure rntacl. Results indicate that both components are necessary for in- terferon induction and that the secondary structure of the polymer is no( critical. Pitha, P. M. and Cerrrr, W. A. Nature New ewlory 2)4:105-106, 1971. Ollver aupport: American ('ancer Society and U. S Public Ilealth Service Frorp the 1)cparlmenta of Medicine and Mrcrobiology. The lohns llopki,a Unrverrity Schrxrl of Medrcine, Bdtiniore. SF.I.F.Ci1VF INHIBITION OF VIRAI. Fl1NC'TIONS: THE ANTIVIRAt- A(7TION OF INIERFERON ANl) STREPTOVARI('IN This is essentially a review artick describing and discussing several of the advances that have taken place, as well as some of the still unanswered rauea trons, which concern Ihose working in antiviral chemolherapy. Recu.gninng that both cytolytic and on(olIenic viruses may have common mechanisms of protein and nuckic acid synthesis although they cause antithetic effects on cells, the authors suggest a possibly similar therapeutic approach to thcsc two types of viral infection. In parlicular, they are concerned with two compouods, interferon IIF) and streptovar{cin (SV), whkh seem to possess both of the ekments essential for broad clinical applicability, namely, specJkity in action and a wide anliviral spectrum. Interferon selectively blocks viral protein synthesis and is considered a major bulwark of host defense in primary virus infection. Streptovaricin inhibits the RNAakpendent DNA polymerase, present in all of the RNA tumor viruses strxlied Ihru far and apparently euentiai For lumorigenesis. Not only does SV decrease the efficiency of RNA tumor virus oncogenesrs without a measurable eflecl on normal cell growth, but it also bkscks replication of vaccinia, a cytolytic DNA virus. TTrus. SV appears to act specifically on vuus-irsduced even/s, reflecting a specificity mN inherent to nsoN antitumor drugs Aho discussed at knrth, are the prnsihle mechamsms of IF induction nd the evidence /or its suhuml structure in the human, as well as the action of SV as a reverse Iranscrrptase inhibitor Certrr, W A, Prtha, P. M, Brocknun, W. W., Borden, li C. and Marshall, 1 . W. AlrJurnr SIOI:Id) les, 1972 Ot6rr .upp..rl: I1 S Public 1lcalth Srrvice, Jane ('o(hn ( hrWs Fund, and American ( anccr Srxaty, Maryland Ihvrsion Fnxn the 1)cparlmcnts ol Medicine anJ Mrcrohiulo[y. Ihc l..hns Ilopkinm llnivcrsdy Schcx)l of McdKrne. Raltrmurc. 19 IM

(:AP 111N('!Il)NS IN NORMAL ANL) TRANSFORMP.1) FIBRC)BI ASIS IN ('1111tIRE Intcrcellular contacts are essential for various functkxul phem.nxna Fkc- trophysNdog.cal studies of cacnable and non<tcrtabk systems ha~e demon- slralcd Ihat rntcrccllutar contacls can result in the cslablishment of luw.resist- .nce parhways which ionrcally couple the cells Studies of the povrhle slruc- tura) basn for the bw resistance palhways, have reveakd, in ccrt.rn orCannms, scptate and gap junctions between inver/ebrale cells, and gap /unctirvss hetwecn vertebrate cells ('umbirscd morphological and ekctruphyswlugrcal atudres of escitable cclls imply that the tap jrrnction is the low resuunce uruaurc. 'lhe aulhors report the unambiguous ideMiAtNiow of gap fursctions betwten cells in rrsoewlayer culturn of txsth rsornul .nd Row sarcoma virus transformed fihro- blas/s, known capable of ionic couplinlL Ihrough the use of conventional thin ssclions, lanthanum usspregnation, and frt+eze fracture. No aon occludens couk/ be identified. Pinto t)a Silva. P and (3ilula, N. B. (Fnlrwbrt, fl. N 1 f,rrrlmrwul Cell Rrrr.rrA 71:)9)-101, 1972. OtArr .rrrwrfr National Inailuta of Health, Gray Institute for Molecular Biology. lane ('olfin ('hJds Memorial Fund, Atomic Energy Commrasion, and U. S Public 11ca)th Service. From the Department of Medicine, l/niversay of California Schoo' of Medi- cine. San Francisco, and the tlepartnscnts of Botany and Physiology-Anatomy, University of Cahfornu. Bcrkeky. 1HE CLFARANCL? OF BFNIC>(A)PYRENE ANL) FERRIC OXIDE fROM MOl)SE II/N(;S Llersre(a)pyrene (BP1. found in tobacco condensate and smoke of diversified organic matcruh, r one of several airborne substances which are potential or povcn carcinogens and contnbute to the increased incidence of pulmonary diseases which have become a major. world-wide problem. The metabolism of BP hu been eslenuvely studied in laboratory animals and one researcher has shown that a saline suspension of the compound adsorbed onto ferric oaide cao snduce cell carcinoma in hamster lungs. Several mechanisms for removal of particvlalcs from the alveolar region have been proposed. lhe general opinron, however, is that macroplsates pha6ocytixt the p.rticks and either migrate to the lymphatic nodes or are Iransporled by the intcrsiitral fluid to the terminal bronchioks, cilrar motiong then voiding the material thrcwrgh the trachea. Although this usually happena very slowly, only tracey of BP were found in hamster lungs I S days after a single trcatnsent. Since the degree of carcinogenicity of any wbslance apparently depends upon the mo.k of contact and the species of animal involved, the way in which drRerent species eliminate a substance from the lunp may have an important bcaring upon its ability to induce tumors lhis report presents the inilial results of studies on the clear- ance of BP and ferric owide from mouse lunp lhc data reveal that BP is eliminated from nMWSe lungs faster than Irorn hamster lunp, arnd that Ihere sre two distinct skarancc ratcs Iw BP and ferric o.ide, the (ormcr hrrns slmrnt cumpktcty rlhmnaicd by the loruth day whrk 70% of the l.ttcr was still presrnr s/ter sw.c week Ihc rare ddlcrences for the two com)xMrnrls suggest 20 thal two inrkpendent renw)vnl processes are in opcrauon Apparcntly. BP r wtubilrted in thc lungs and met.Mditcd either by rnlcr.tdral thssue or hver. The presence of an rrrducible BP hydroaylating enzyme in various tnsues has been rcpurted, and it may be that the speed at which it can be rrsduced and its specific activdy plays an important role in determining the BP cucinngenicuy in the mouse lungs. Further esperimenution to determine the relatronshrp between drnage and clearance rate is necded, as well as the study of BP meub- ohsm in mouse lungs which is now in prugress. lio, W., Benlon, M. and Fusr, A. Procrrdmer of the Wrrrrrn Phnrnrardoty Soclrry IS'SE 60, 1972. From the Institu(e of Chemical Brobpr, University of San Francnco, Sa. Francisco. l)1SSIiMINA1F.t) RIIABL)nMYOSARCOMAS FORMFI) IN KIIi-IENS BY ('1/1.111R1it) III/MAN RIIABIK)MYSARCOMA CELIS This paper describes, for the first time. the successful lransplanlation of cultured human rhabdomyosarcorna cells in kittens by prenatal inoculation. T( e cultured human cells (RD cell, line AI2) were inoculated into the fetuses of three pregnant cats at approximately 40 days' Rntalinn. lhree o/ five surviv- ing kittens from two /iuers developed disseminatcd rhabdornyosarcomas 16, 36, and 60 days alter birth, respectively. One full-grown stillborn knten of the third cat had rhabdornyosarcomas in the liver and thymus. 7he tunwn in all ki//ens loasked like the original rhabdomyosarcoma from which the RD cell line was derived. Cell lines derived by tumor cell isolation from three cal lurnws consrslal o/ Iwo cytobgic typcs rraemblingthose of Ihe original lumor-polygonal cells and strap celh. One cell line was inoculated into (ctal cals. and rhd+domy- osarcomas composed of human cells formed in two ol three surviving kittens .t 1) and 47 days after birlh, respectively. Although the parcnt R!) cell kna containcd no detecubk C-type virus particks. two cat tunwrs and one cell Irne derived from one of these tumors contained C-lype virus particks of unknow• origin. McAllisler, R. M., Nelson Rees, W. A., lohnson, E. Y, Ronry, R. W. and Gardnrr, M. S. /ournol o/ the Narbnd Cancrr INIIIYrr, 17(I):60)-b11, 1971 , Other support: U. S Public Heafth Service and National Cancer Institute. From thc (kpartment of Pathology and Pediatrics, University of Sourherw California School of Medicine, Childrens Hosprtal ol l.us Ankclcs, tos Aageln, and Naval Bromcdical Research l.aboralory, University of (-ddornia. School of Public Ilealth, Oakland, Cal. IN VIVO IItiMAN HAMSIER SUMATIC ('Ell. FUSION INIII('ATEL) BY (;Ll/('OSF.6PIIUSPHAIE UL:IIYI)R(X:ENASE AN!) IA('TAtE UEFIYI)R(X:ENASE PRUF11 FS A human hunslcr hybrid, predominantly hamster hke in character and behaviur, has L.ecn produced !n riro In work «portcd hrrc, Uansplantarwrn of a human lymphorna to the check pouches of uneondnwned, adult golden hamsten 21

resultcJ in permancnlly Iransplantahk lumors which Sruw prugrc.avcly and kill their ho.ts Ihrs lunwr syslcm, (iW-17fl, has a harnsler spccdic lactate Jchydrorcnasc r.a•nryme mobility patrern and both human .rsJ ham.lcr Clu- crne 6 phusphatc JrhyJrogcnase enzyme pruliks when proprg.rtcJ in the hamster or in rnco, thus suggesting thal GW-47N u a human hamster hybrid. GalArnMrt. O. tl1, 8han, R. D and Pavia, R. A. Cancrr Rr.rorch )I(lil:l l~e-IIS2, 1971. Other aupp..rf: National Cancer Insldule and American Cancer Socicty. I rom the Ikpartments o/ PNholoRy, Temple University School of MeJrcine. PhiLJelphia, anJ University of Pittsburgh School of Medreine, Pittsburgh. ALlh.RAT1UN IN Ct:t.l. PROI.IFERATION IN MOUSE 1.UNG FOt.1.OWINO I1RF1t1ANE EXPOSURE. 11. FFFtiCtS OF ('IIRUNIC t!XPt)SURE ON 1FRMINAI. •RONCNIOLAR FPt111F1 t(1M In this sludy, an attempt was nsrk b oulline the cycle time of dividing cells in hronchrolar epdheliurw of sormal wsice and compare this w th the cycle time in hyperplasuc eprthelium of wuce chronically eaposed to urcthane. For this purpose, animals treate.l for 10 weeks wnh drinking water containing 0.1% urethane and thew controls were injected with sIl-(hymidine; wtor.diographs were made of lung hssue and mean Rrun counts of labeled nuckr in terminal hnwrchrolar cpithchum compared in the control and urethane-treated groups. In conuoh, the dechne in mean grain counts of lahekd daughter cellt between 24 houn and 4 days after '11 thymidine injection was compalrble with a manmum cell cycle hrnc of about 60 bours. In conlrast. the hypcrplasrrc hrorschrolar eprthchum of the urethane treated animals showed an ekvated labeling irs.ka and dclKKnt pruductr..n of labeled cells over the 6 day pcrKxl a judged by decline in mean grain cnunu lAese findrnRs were interpreted ss showing that the hypcrplasia and high labeling indes dNd mN rlpreunt (aster turnover or shurteneJ cycle hut reflected an increase in cell cycle Irrne or of population nenewsl time. Kauflmon. s L.. The American lournaJ of Patholory 64()):3)1-S)S, 1971. From the F)epartmcnl of Pathology, State University of New York, Downstate Medical ('enkr, Brooklyn, N Y. A1.1F:.RAi1ONS IN CEt.I. PROIIFERATION IN MOUSE LUNG FO11.OWIN(; IIREIIIANE EXPOSURE. Ill. EFFE.('IS OI' CIIRONIC I-XPOSURE ON IYPE 2 ALVEOLAR FPIIIIFLIAL ('F.t 1. In thn paper which is part of a continuing series, the auth.rr eaamines the eRect of chronic urethane esposure on proliferation of Type 2 alvcolar cpithchum in mke by rneam of autoradr)paphy. e'ontrol animals and thrise eiposeJ /or 10 weeks to urcthane in drinking water were injeclcJ with 'tl IhymrLne anJ sacrnfiaeJ at rnrrrvals ranging from 10 minutes to 7 days Mean grain aounH of lype 2 slverAar cell us the two grewps showed that the cell cyck tume ul tesl mice waa pro6mlcJ whcn compared with n esumareJ 22 hcnir cyck (or ccx+- Irols; Ihis was accompanied by  fivc(oW increasc in Lncclrn6 ux1ct in leu anim.ls. ll'ouArnrrn, S. L. 7hr Arnrricon lownuf o/ PuthulnXy htl(2):)17-)26, 1972 From the Ikpartmcnl of PNhulotY, State University of New York, Ikrwnsute Medreal ('enter, Brooklyn, N.Y. ('FI.1. ('YCLF 1)t=.PENDFNT IMMUNE I.YSIS OF MOI ONI:Y VIRl1S- 1RANSF(/RMFD I.YMPII(K'YItiS: PRFSt.N('E OF VIRAI. AN71(;I:N, ACCt:SSIBILIIY 10 ANIIBOUY, ANU COMPt'EMEN7 A('IIVAl1ON "The espression of Moloney kukcmia virus on the surface of a viral- induced lymphoma «ll, availability of the virus to anMi-vual antihody, and the nature and eslenl of activation of the compkmenl syslem durinR the cell cycle were studied iw vitro. Viral antigen was present on Ihe cell suwtace, accessible to aqtrlwwly, anJ was able to aclivale compkment in the presence of antibody throughorq all cellular growth phases, whik cytolo.icny was conflned to the (ir phase of cell growth. In addNwn, when cells were arrested in nsetaphase, virJ antigen could be demonslrated on the cell surface by immurwfluorescence, and buddmg virus was seen by electron microscppy. All nine components of com- plement were activated on the addition of antibody throughout the cell cycle. Additional esperimenls indicated that in the presen.e of ansrbvdy. C) and/or ('1 were immunospecifk.lly brwrnd to viral-induced IYmphoma ce11s throughout the cell cycle as a result of complement .clivalion. These results indicate that the inability to Iyse the cells in the presence of speci6c anti viral antibody ud complement during the loprithmic phase of cell growth is not due to the lack of ecpressron of Moloney tirus anligen(s) on Ihe cell surface, inaccessibility of this surface antigen(s) to amibody, or (ailure to activate the complement eflccror system. lernrr, R. A.. Oklstone, M. B. A. and Cooper, N. R. rroce.eins, of rhe Nationaf Acdrrny o/ Scirr.cei, U.S A. 6tl(10) 2581-25(f6, 1971. Other aupporl: U. S. Public Flealth Service, National Multiple Sckrosis Sucicty, and U. S. Atomic I:nerp C'ommission. From the Ikpartment of E.perimental Pathology. Scripps Chnic asd Research F--uundalron, I.a lolla, C'.I. 1?Ci1MA7lON QF ('EI.1- NUC'LEI ('UT AT lHF SIIRPACf: OF 71SSUE SEC. t IONS rH thymiJrne is often used to estimate the rcplKitrvc potenwl of a cell population, measurcd as percentiac IahckJ nuclei in sururadwrgraphs Several diltKOllres, howevcr, prevcnl the absolute quanutatiun u( incorporated pre- cursors fruns sutoraJrographs of thick scclMns (1) triuum crours weak (t psrlr.ks with IimilcJ path kngth and is thus nKVsl susceprd~le to sel/-al.urrprwn; (2) any ddlcrences in the Jry mau per unq area will affect the nature of ncc Jar• when grain c.n.n1 compaursuns are to be made among Jdtercul crll typc., since the sel( absorption coeflkient increases with rncreascJ Jry mass, dccreas 22 21

ing the autorsdiographic efficiency; ()) when ouckar diameters vary among the ccll populalrnns of diflerent tisaue sections under comparison; in a thick aectiexr, the probabdity that the large diameter nuckr will fall within the tril.um- uWoradrographic range is greater than that fcw small diameter nuclcl, possibly d.stor,mA results A simple method is dexrrbed lor estimatinA the numhcr of euckr rn a tisuut scction which sre cut and eaposed at one of the section surfaccs. TAese can be easily eakulated when section thickness and nuclear diameter are known The method 'n most useful when percentage nuclei labeled by trituted prccurson are to be compared among various cell populs- ticwr with diflerint nuclear diameters. Modak, S. P.. I ever, W. E. and UppuAur(, V. R. R. (1-eucArenbrrter, C.) Erpcrlmrws.f Crff Rru.rcA 70(2):IAS-Kfl, 1972. Other arpperfr Swisa National Fouodatiow .nd U. S. Atomic Energy Corn- minins. From the Department of Cy1oclewristry, Swis Institute for Esperimenul Cascer Research, IAwa..e, Swilaerlaad. MYELOID I-EUKEMIA IN 7?IE RAeB1T (ORYCTOLAGUS CUNICULUS) TTThis is the Arsl de+eriplion of a case of myebid leukemia in thc rabbit, a henulopoiNie neoplasm never hereto(ore rrported ia this animal. This particular case occurred ia a I).S-monthold slrsi. lll,p msk and iu fealures were dis- 1inAuuhabk from hereditary lymplrourcama by cell lype, organ im•olvement, and distribution of tumors. The investiAslors are proceedinA with genetic studin rn a. attempt to identify the Acnc(s) conferring susceptibility to mycloid kukemia, and to determine whether an oncogenic (RNA viral) genome is Involved. Mekr, ll., Fo., R. R. and Crary. D. D. Cawrrr Rru.rcA )2(6).17d3-17[7, 1972. Olhrr.rppert: National 1nalNutesof Healt)t. From the lacksoe l.aboratory, Bu Harbor, Me. RNA TUMOR-VIRUS ANTIGEN EXPRESSION IN CHEMICAI_LY INDUCED TUMORS. VIRUS~'iENOME-SPE.CIFIED COMMON ANTIGENS DETECTEI) BY COMPLEMENT FIXATION IN AIOUSE TUMORS INDUCED BY )-METHYLCHOIUN"THRENE Tl+is report describes the lumor-inducing talects of a single 150 rg dox of )-methykholanthrene (MCA) given subculaneously to weanling rnice of 12 inbred and four noninbred atrsins. All mice of the 16 slrains were uealed at four weeks of aAe. Mice wert essmined weekly for eight months for tumors at the injection site and for other neoplurns. The MCA-induced tumors, which were nearly all subcutaneous sarcomas of mesenchymal origin, contained com- pkmcm Asing antigens reactive with rat anteer. sekcted lor high titcrcd re- acticxts to the gruup apccifk (gs) antigens of the (' type RNA twnor virus. Since mxmal nxsciKhymal tissues (musck and subcutaneoua) did not reveal p I antigcn, the concurrent aclivalion, or derepresaion of phenotyprc eeprevion of viral or viral-rcl.ted antigens in many of the tumors, suggests that oncogencs of ('-type RNA virus genomes have served ss specrfic determinants of the in. duced cancers Bccause other studies ahowed that the virogenea and oncogenes ol the C-type RNA viral genome are vertically transmitted as repressed genomes, probably as a parl ol natural Aene rnheriunce, it is hypcwhesired that the carcinogenic scti(us of MCA is achieved by directly or indirectly derrpressins the endugenous RNA tumor virus oncogenes that must be in all mouse cclls. Whitmire. C. E.- Sakrno, R. A., Rabetein, L. S., Huebner, R 1. and Turner, H. C. (Mirrobiologkd Arrociarn. Inc.) Journal o/ rAr National Cencer Instlrrrrr d7(6):1211-1265, 1971. OtAer supportr U. S. Public Health Service. From the Department of Viral Chemical Oncobty, MicrobiobAical Asaociates, Inc., and the Vird CascirroAencsis Branch, National Cancer Inuitute, Natio.d Inslilutes of Ilcallh, Bethesda, Md. ACTIVATION AND ISOLATION OF HAMSTFR-SPECIFIC C-TYPE RNA VIRUSES FROM TUMORS INDUCED BY CELL ('1/1.TURFS TRANSFORMED BY C19EMICAL CARCINOGENS This paper presents evidence that Ahe 1alent or rep.esaed hamster-epeclAc kukemia virus (IIa1.V) reswme may be widely disseminated in hamster colonieu, but can be activated and isolated only under certain conditions. Cell eultures of Syrian hamster embryo were treated (or seven days with 0.1 pA/mI of 1he chemical carcinogen )-melhykholawlhrene, or wi/h 0.1 or 1.0 pS/m/ of cert.in fractions of cigare(te-smoke condensate dissolved in acetorse and diluted i. Fslk's Minimal Fssential Medium with 10% fNal-calf serum. After the initial 7day treatment, the chemicala were renaved permanently and the culturts were subdivided as needed. Cell cultures transformed by methykholsn(hrene or by ciAsrelte-amoke (raclions 6•nd 9 produced malrAnaM tumon at the siN of inoculation after 1)-110 days. New cell lirses were established /rom repre- sentative tumors. Although the cell lines were negative (or infectious virus before inoculalion into animals, hamsler-spccifk C-type RNA virus was isolated from lumors or from cep lines derived from Ihe tumors. Since inlectioua C-type viruses are usually no( demonstrable in hamster tissuea of normal or tumor o.rgin, it was concluded that the chemical Ireatmenl and activatiow of the viruses are related events. Frceman, A. E., Ke11oR, (:. 1., (3ilden, R. V., I.sne, W. l'., Swain, A. P. aed Huebner. R. 1. (1Nkrobloloeird AssoriorrrA fnc ) r.ocrreintr oJ rAe Norlonul Aralemy o/ Sclrncr., (/ S A. 6E(10).?)e6 2)90, 1-I71. • OtArr supp..rl: National ln.litutes of Hedth. !'vurn Microbiological Associates. Inc , and nce NatKmal ('.nccr Inuiruu- Bclhesda, Md . flOw I ahoralnrKs, Inc , Rockvllk- MJ , and I a+rcrn Marlcdnll and Nutrhional Research Urvrsion, Agrrcultural Research Scrvrce, 11 S 1) A, Philadclphia. 24 25

RNA 111MOR VIRUS Rr ANTIGF.N AND TUMOR INf)UC1ION BY VARIOIIS /K)St S(1F ) MI:.111Y1 ('1I(N.ANl1IRF.N1' IN VARIOUS SIRAINS 01: MI('E 1RFA1F:1) AS WIiAN1.INGS It has been wRRcstcJ that chemical carcinogens induce tunwrs by direct or indirect Jereprcuron of endogenous oncogenic informaticsn pruvrlcJ by in- hcnlyd, largely covert. (' lype RNA tumor viral Senrxnes postulated to be prexnt in all vertebrate cells. In thest sludies the dlect of various d4nes of 1 methykholanthrcnc on suhcutanccxn tumor induction and the occurrence of the murrnc ('-type RNA group specifk (fr) viral antigcn in tumor tissuet were eumincJ in weanling mice of ti genolypically diRercat suains. Tumor incidence anJ latency, and the occurrence of Br antiBert in the resulting lumors were compared to show the relationship o( these rnponses to varying doses of the urcinogen nJ the natural espreuiow of the C-type RNA tumur virus Lenome of the dillerent niouse strains. Tumor iecidence was related to the ckne of ) mcthytchcslanthrcne, hut tr antigen was indepcnJcnt of the dosage •nd refkctcJ ns natural e.presuon in this mouse strain. Itntopathuk>eical csamina- tMrn showed no rrtatrrn of luwsd type to c.rcrnogrn dosage or atrain The marrrity of the tumors studrcd were urcornas. TAcse results confirm carher oncs which sugcsreJ that the gr antiges e.pression induced in tumors is de- pcndcnt on hrxt regulatory controls and that such controls of virotene (tr) antigen and oncogene Itumor Induction) espressions of C-type RNA viral gcnome are irdepcndcmly affected by  c.reinogen. Whrtmire, C. E and Sakrno, R A(MkroAiolorical Aiioclarrs, lnr.) ('ar.rrr RruucA 12(6) t t 29-11)2, 1972. Other support: National Cancer Institute and ll. S Public Health Service. 1'rom the Ikpartnunt of Viral<-hemical Oncology. Mrcrol.iological Associates. Inc . BethcsJa, Md INIIIBITION OF CIIFMICAL ('AR('IN(X;FNI:tiIS BY VIRA1. VA(( INIS The demonstratcd high prevaknce of ttoup specific antigen espression of the type C RNA munne leukemia viral genome in chemically induced tumors in mice supports the concept that endogenous RNA virus depression or activa- tion provides a significant detertninaM of ehemicalty induced cancer. The feasibility of inhiAaing chemical carcinorneaia by vaccines prepared from these viruses was studied in two genotypicslly different mouse strains. Mice were vaccinated at 4 weets of age with a single inpction of formalin inactivated virus combined with Freund's complete adjuvant nd challenged suhcut.ne- ocnly with 150 rs ) methykholanlhrene at 0 weeks of age. The mi;e were observed for whculaneous tumors at the sile of inoculation for a period of S nvonths. Rauscher leukemia virus vaccine reduced the incidence of ) mcthyl- choianthrene-induced subcutaneous sarcomas from 78% to SOrA% in the BAIB/ c('r mouse IP < OS). lwo inactivated vaccines prepared /rom raJratton kukemia vrrus and a wild murine leukemia virus derivcd from a) mcthyl- cholamhrene tumor reduced the incidence of sarcomas from 96% to )) and 17'f,, respcctivrly, in the ('5781 /6 mrwse (P <(X)I and P. 01. re- spectively) Iheu rcductions in tumor incidence by virus vaccines hclp supluul the conccpl that typc C RNA viruses servo as delcrminants of chemicaliy inJrccJ cancer. AJJitiunal slrKares ul wch viral vaccincs in thc arc.tnscnl and prcvcnuun of canccr arc uccess.ry. Whitrnire, (' F: and 1luchnrr- R. 1. IMic.o6iuluKicul Arrorrurrs, Inc.) .Icirru r 177.60 61. luly 7, 1972 Orlrrr sup/srrrt: ll. S Public Health Scrvice (National ('ancer Intutute). From the Department of Vual (-hemical Oncology. Microbiologrcal Associates, Inc, and the Vual ('arcinoLenc+n Branch, National Cancer Insutute, National ImUtutet of Fiealth, Bcthcsda, Md. INIIIBITION OF ('NEMI('A1. CAR('IN(X;ENN1tS BY VIRA1. VACCINES l:.otenous interferon inTrbitcd the )-melhykholantnrene ()-MC) induction of suhcutancous fihrosarcurnas and of lung adenomas in ('F-I mice. None of the 26 anrmah treated wnit interferon developed multiple lung adcnomas. whereas M out of 1I1 ue.tcJ with pMnphate huAered sahne (PBS) developed the (bmors. 1 hc inci.knce or tnre of rr antigen dctccted in aplccns by the complement ff.;rtion test 1 final lissue Jdutwns of 1:20 to 1.140 JMl not differ in the treated and untreated groups. Although the mode of action through which interferon prevents chemical eareinorenesis is unknown, the authors feel that the following mechanisms of anliviral and/or cellular eflects of interlerow nwra be conswlercd: (1) inhibition of the growth and multiplication of both tumor anJ normal cells; 1_s) nonspecifie enhanfement of macrophaffie activity and lymphoeyte cytdo.icNy and/or (3) viral snhibition of a postulaleJ vital inlermeJiale, such as the endogenous oncogenic type C RNA virus, that may be responsibk /or chemical tumor induction. Sakrno, R. A., Whitmire,`C. E., Garcia, 1. M. and Iluehner. R. 1. IMicro- hiuluKit ul Auoriorrs, lnc.) Naturr New Brology 2)9(tlR):)1-)2, 1972. Otber support: ll. S. Public llealth Servict (National Cancer Institute). From the Ikpartment of Viral Chemical OneoloRy, Microbiological Associales, Ine., and the Vrral ('arcinotenesis Branch, National ('ancer Intbtule, Natio.al Inslawtes of Heallh, Bethesda, Md. SUS('FP1111l1.11-Y OF ('IIROMOSOMIS FROM PAIIENrS Willi I)l)WNS SYNDROME 10 7,12-DIMtiIHYl.BtvNZ(a)ANIIIRAClN13- INI)U('ka) ABI:RRAIIONS IN Y/IRO TTe chromosomes of patients with Down's syndrome are signiM1camly nuuc suscepubk in vitro to damage by UMBA; this increased susccptrbddy n not Jue to a deficrency in ability to repair DNA damage. In this uudy, the elfcals ol 1)MIIA on the chroaxnomes of seven patients with Iko.vn's syndrome and ten healthy volunteers were sludreJ. ('hromatwl gaps or hrca\s compnad the vast maNsrny of ahcrrations proJuceJ in the chromrnrxnes of both group. Snull rwmhcrs uf IlnChr(Mlalld eschantes and Jaemrrc chrunrrsa.mes were alsu ohs.rveJ. Ihc lymphocytes of patients with 1)uwn's syndronse were no/ Jcficicnt in thcu bihry to rcpair DNA damage Induced by uluavic>act light or 4 mUUyuuKrline N oxK)e anJ, at the Joscs used to produce chromuw.nul shcr- rations, 1)MIfA JiJ not significantly inhibit either repbcauve I)NA synthesis 26 27

or the repair of JamaRe induced by ultraviokl (ight or 4 nitroquinc(ine N naide in n.amal lymphucytes or in Ihose from patients with 1)own's syndrome. OMHA did aN srrmulate unscheduled DNA synthesis in the lymorocytcs from patients with t)trwn's tyndrorne or from normal controls. O'Bricn. R l. , Poon, P, Kline. E. and PrAec, 1. W Invrna-hond lou.na/ o! ('ancer (42) 202-210, 1971 Other support: lohn A Ilarllord Foundation. Professional Staf' Association of the I os AnRAcs ('rarnty-llnivenity of Southern California Mrdical Cenler, and (1 S Public Health Service. Front the 1)epartment of Patholoq. Uwivenity of Southern Cslilorni^ School of Mcdicrne, I.os Angcks. DNA RFPAIR 1:O1 1 OWINO EXPOSURE OF li(1MAN LYN PIi(X'Y1IS lO 4 NIIRO(jUINO( INE-I OXIDP. lhe ca-clnolen, 4 -nlroQuinoline loside (4NQO) is tnown to induce unscheduled DNA synthesis when admia'rstered to a variety of mammalian cells, including human lymphocytes. The demonatntion of unscheduled DNA synthesis in a cellular system, however, does not prove that suclt a system is under`orng DNA repair. It is raecewry, to show that, at the time of the un- schedukd tynthetis, -eplrcative DNA synthesis is not oecurring, or that incor- porstion is taking place in DNA which is not undergoing rephca'ive synthesis. Such evidence can he obtained by demonstrating (1) unschedukd DNA syn- the%n in the presencc of a-nown rnhrMtor of rep(rcative synthesis such ^a hyJroayures 111111 or (2) urcorporatson into DNA known to have been previ- ou%ly rcplresred and whKh as not in S phase lAu paper repocts the results of such eaperunicros, usrng freshly obtaHxd human lymphocytes from venoua blood DNA danutc is produced with IN(x) and ultraviolet radiation (l1V). and DNA repair is dcnNMn/sted That study confirm the conclusion reached by others that 4N(jO inducn unschedukd DNA synthesis in human cells, and it shows that this is a function of both the concentration used and of time. In addition, the authors provide strong evidence to support the hypnthesn that it is indeed repair DNA synthesis which follows the administration of 4NQO to mammalian cells. lacol.s, A. /.O'Brxn, R L. Prlc-, 1. W. and Paolilli, P. InrernrorJomal lournal of Crscn 10:1 1 t1-127, 1972. Other srpport: John A. Hartford Foundation, Mary R. Wright Estate and U S Public Flcdlh Servioe. From the lkpulmenl of Patholop. University of Southern California School of Medicine. I.os Antek1. INFI UFNU DFGI I ORMONI OVARICI NFLI.A CAN('FRO(:FNF-SI P(11 MONARf? l)A II)RA7INA SOLFATO IN TOPI C)I+h/('b/Sc The (')llh/('b/tie mice used here have a bw inciJence of prJmonary tunurrs (p r) 111a11y admrnnlratron of hydra:ine aulphale (h a) at a dose rste Of 11 m( r• r.-r.l .1 I)It mg- rncres-cJ the utirJersce of pt's, and their --1-cr IK-,,..r as L.IS...r inra. r vugrn maks :h'1L and 1, (cnules 48% 21 and ); gonadcctomiteJ maks 4% and 1, females 19% and ?; breeders )91i and ); forced breeders 1S% and ); pseudopregnsnts 44% and 4 Flrstobgrcally, the p t's inJuced by Is a. in intact vi-gin and gonsdeclomiied mice were 93% adcnomss and 7% carcinomas; in breeders, forced breeders and pscurbpre[- nanls the percentages were 68% and 32%. 7he higher incidcnce of Is a-induced p t.'s and the increased number of p 1.'s per female mouse in comparison to that of males, and the greater morphological malignancy of these tumors is breedtrs, forced breeden and pseudopregnants in comparison to intact viriie and gonadcctomired mice, conf(rms the implication of ovarian hormones in Is s.-induced pulmonary Oumwigenesis in p t.-resnunl CG11b/('b/Se mice. Biancifiori, C. (Srvcrl, L.) "v. Anor. Pat. Perrgia ] 1(1):5-17, 1971. Other support: Anna Fuller Fund. From the Divuion of Cancer Research, Univertity of PeruRia, Italy. TRAPIAKII ISOOENICI IN OSPITI ADULTI E NEONAT7 DI TUMORI POLMONARI tNDOTiI CON IDRAZINA SOLFATO IN TOPI BALB/c/Cb/Se: STUDIO ULTRASIRUTTURAI.E The flnl 22 transplant generations of • lung tumor induced by hydrasiae sulphale in a BAI.B/c/Cb/Se mouse and Iransplanted in newborn and adult syngeneic hosls, have been studied in the ekctron microscope. As peviously reported for the primary tumon, the transplanted neoplaslic cells conacrvod all the features of the normal alveolar type B cells from which the tumor originaled. Of the three types of viral particks obaerved in the primary lumors. that is tubular, intracislernal A. and C. the tubular particka dis^ppcared and the intrscisternal A particles were considerably neduced in number whik thcre was an increase of C particks, particularly in the transplants carried out in newborn hosu. C particles have also been observed in a lung meNSslaan of a mouse with a transplanted tumor. No virus was seen in the normal lung liwr. lhese data confirm the derivation of rrwuse lung lumora from type IN alveolar cells and suggest that the neoplastie transformation of these cella and their transplanlation in newborn hosts may provide favocatrle conditiosu for C particle replication. It has not. however, been possible to establish ^ny eliololti- cal relationahip between the C particles and the lung tunwn. Bueeiarelli, E. (Severl, L.) Lar. Anar. Pat. Prrsitla 31(1):19-31, 1971. From the Division of Cancer Research, l)nivenity of Puugia, Italy. SENSIBILITA Al. METI(`OLAIJTRFNE DEG(.1 EPITEI I UIiU.'AI.BERO RESPIRATORIO IN T'OP1 BALB/uCb/Se The acnsirivity to merhykholsnthrene (MC) of bruncMolo alvevrlar and Irachco brunchul cpitheb• has been investigated in MAI B/c/('h/Se mK• Fragmenls of lung tissuc, large bronchi and trachea were unprcgnarcd with M(' ^lone or miacd to talc sterdc powder in the conccnuations u( 1/10 and 1/1(Ml. The impregnaleJ fragments were then uansldantcd into the subcuuue- 29 I

uJcnuaras, uus lat pads of synKcncic h.nh MC causeJ the Jc.clupnscnl of arypical adcnomas, nr malr6nant "aderK+mas" Irorn hrurKhwln alvculJr cprehcha and pr„liferat+om, atyprcal prnh(ctaUOns with squamrHrs nh•IJpla.rJ. ur syuam- out mclaplasiu. m sl(uJnMN/s ccll carcinomas front Ira.hcu hronwh+al cpuhcl+a 1 he frcyueniy rd vansplants slww+ne hronchwdo alvcrdar aJcrn+nus or tuchco- hronch+al tunKUs aftcr treatment with decreasing conccntratruns ut M(' was as lallows M(• al.+nc; aJcnomas 40%, lumors 9(1'T, ; MC in tak pnwJcr 1/ 10; aoknr+mat S1'X,, tunK.rs 7A'x; MC in tak puwJcr 1/I(K); adcnumas 64'X,, wnr+rs 14% It is concludcJ that the sensitivity W MC of hron.hurk+ alvcolar epdheha is mrxh h+Rhcr than that of trachco-brorKhiJl epithelia lluwcvrr, the laUer are not rclractury tu the carcinorn as can he sccn by the alnus.t consunl tumor growth after rmprcgnation wilh MC ufune. tiquartmi. F and B.drs, O B. (Srvrrl, L ) l av. Ana( Pat Prrurro )tll):)3-36, 1911. 1 rom the Ihvruon of ('anccr Research, Ilwivenity of Pcrugia. Italy 1l1MORI POI MONARI E MAMMARI DA IDRAZINA SOI FA 10 IN IUPI HAI.B/c/('b/Sc GFSTANTI FORZAIE E PSEU! iRAVIDE 1)sc incidcnce of pulmonary tunwrs (p t) in BAl.B/c mice was 20% in Forced hretden and d% in pseuakrpregnanls; the number of lumors per mouse was I and I. Flntologically att lumots were aJcnomas FlyJrarnre sulphate (h s) raised the p t incrdencc to 96% in forced brecden and to 95 ;. in pscudopregnams, rhe number of tumors per mouse was 10 and 1'_ 1lntulugi- cally, in the fnrccd hrecdcrt, 57% were adcrnxnas and 1)% carcuw,+as, whdsl in [ht pseudoprcgnnts the percentates were 60% and 40% Ihcsc results confirm the influence of endotcnorn ovarian slimulation in h s mJrKCJ lung carcinogenesrs in n+re Mammary lumon were rot ohs(rvcd in the cunuols nor in the h s treated p+euJoprcgnants but h s irxhKCd these in )8% ol the forced btecdcrs. lhe Mstolollrcal piclurc was of urctular tubular, puly6onal solid and papillary cystic carcinomas. lhe induction of mammary tunwrs in the h s.-Ireatcd forced breeden may be related to the horrsxsnal /actur anJ to kngth of time the carcinogen remains in the ducts. Biancifiori, C. (Srvnl, L.) lav. Arw. P.t. Prrurl. )I()):79-90, 1971. From the l)ivision of Cancer Research. l)nivenily of PeruRia, Ilaly. PRI:SFNZA 1)1 AN11(iENI GRUPPO-SPF('IFI('1 I)F111i PAR11('111E C NFI LA FASI'. LIO(IIUA L)1 Tl1MOkI AS('(Ili Dla. 1O1'O ImmunoJ+Rrnion slrxlics for the prtsencc of typc (' partick grrarp specific antrRcn% were cauried out on the IwuiJ component of ascdts tunwrs on the Srh, 1(Nh arsJ 1 Sth day allcr grafting 1 wo lines of a..uca 141111.,11 wcre u.cJ, A11'(' I anJ I hrlKh, anJ }wrth originated in a spunrancuu% mo++.e m.+mmary a~rcrm rna In ncC h#4u+J pha.c ol twNh lumurs the `ruulr v(w'adK' rnt+Ra'ns aplwar early, arc evident un the Sth day altcr IrJnsplJnlJtw+n a+ul havc a IcnJrn. y In ur rrat Jur+ng the I.d-+n1 JJy% Numctuui curnldc,c tylh• (' +hwh .rt fa.rhwtJ by nce na-pla.r+. acll., arc .uNa+nrJ +n Ihc a.citcs hyruJ Anli ccllular anl+h.-dics wcrc alsu .IcmunslrrtcJ in the sscnes I+ymJ, hut rus amr gnwrp sp.a/ic anl+gcn anhhuJres wcrc uh.erveJ Ihn fact sugcesls that the moux rs cumplcttly u>ferant to Ihc +c.urKl antigen krhxchi, R (.Srvrni, L.) I rrv. Anut. Put. Prrugla )1O1.91-102, 1971. I-rom the 1)ivrsion of ('ancer Reuarch, University ol Perugia, Iuly. ('AYPE PAk I1CLFS IN PRIMARY ANI) TRANSPl.AN7 F.l) 1 l1N(i 11IM1)RS INI)U('ED CN BALB/c MICE BY 11YDRAIINE Slll FAIt:: L.I.F('IRON MICROS('OPIC ANI) IMMUNODIFFUSION SIUbIFS 1)espde cstensivic ekctrurs microscopic uuJies, oncogenic vuuscs have rarely bccn obscrveJ in sponlancous or chemically induced mouse lung tumws. Is a previous ckctton microscopic invesugatias. the authors noted vwus par. 4cks nf thc type asuwuteJ with rmMnc kuRcmi: in a number o( tumors trwloccJ by hydraiine sullate in BA) B/c mice. lhut, in view of the possible activation of an RNA onculIenic vuus by chcmrcal carcinugcns in a system othcr than the lympFwrcucular Irssucs, in which such a phesxxnenon has alreaJy been well Jocumented, this observation prompted them to /urthcr invcsugare the drs(rrbution anJ origin of Iheu p.r,rcles in primary lung tumors inJuced in BALB/c micc by hydrazrne sulfate, transplants of ,hese tumors in newborn and adult syntcneic Mnls taken between dsc first and Iwcnty-/oursh transplanl gcneratiuns. and samples of normal tissue from lumur bearing mrct '1 hcse were studied in the ekcvon microscope lor the presence of virus particks; immunodrRusion studies for the' presence of type C group specJk viral antrtcns were done on both transplanted tumors and on normal Insucs of the sarne mrct. 1 he rseuplastic cells of Ihe primary and Iransplanlcd luwwrs retaineJ the typical suuctore of Ihe ccli of o.ipn, the lypc-B alveolar cell Cylindrrcal, lype-(', and rntracisternal A virus earucks were observcd. ('ylrndrr- cal particks were scen only in the primary tumors and. characlersaically, originated from Jark, rramJar, cyst like areas of the neoplastic cells C par- Iicks budded from thc neuplaslic cclls or were secn in 1he in(erccllular spaces in )Srb of primary lumurs, 62 5% of transplanlcd (utnors in newborn micc, and 31% of those Iran+planted into adults lnlracas(ernal A parlrcks wtrt secn in the neoplastic cells of M11'X of the primary lumors, ?Scx% of the /urrsas transplanted into newborns, and in 12.5% of thost grafted into adul(s. In 63 6% of the normal lung tissuc aampks, only intracistcrnal A particks wuc observed. lype.C, trnup-spccific viral antillens were demonstrated by im munoJdltnrors in the tramplanteJ lumon hul not in the normal o.eans uf tunx+r bcarrng mrce. Ihcst Jata sugtesl a poss+blc acuvatK+n uf type(' virus pu6cks in typc-B alvcular cclls by  chemrcal carc+nogtn Oucccuclli, 1: . and R+hacchr. R, (.Crvrri, L L luuw,d rr/ the Narronrd ('uncrr hnrnrutc 19()) 671 678, 1972 I rcxn Ihc Ihv+suun of ('aoacr Rcscarch, l/mversity ol Perugu. lraly NI (Ik(ril ( RP.IOkY APPI AkIN(i ('11 I S(/F /1(IMAN SI (.MI NI AI HR(IN('III llndcr the clcctrun rui.rasuq.', human nu+cosJl cclls Irum the segmental )I 1q

bronchi of aJul,s appcu to he neurouvesory 1 hey have a low cytoptasmic density and cunrirn snull, dense• rncmbranc txwndcd granules l:rAdct cells containing identical cytoplasmic granules are also sccn in the hronchul mucota. 7 he ryrrsrhk ruk of nrurosecrctory type cells in she gersesrs of bronchial carcirsc»J tumors and oat cell carcinomas is recornireJ, as well as their lunclion as chcmoreceptors and in the secretion of peprrdcs and amuses. lhe « lls described in this rcport may serve as a primary or accessory sourcc of goblet cells under ordinary or unusual condiliona, such ^s various disease stutes. If the ncurote•crerory type cells are iwdeed invotved in the genesis of carcinoid tumors and oat cell carcinomu. Aowever, rssosl of the bronchial ,rce can then be considcred a potential site of oriRin. IFrve additional newly-observed bronchial alteratMMs were preaeMCd by M. Marprct (.ont at the Intcrnatiunal Flistochemntry, meeting at Kydo. These are: darhk-layered sur(acc nsucus and two layered mucus droplets in cpithclium, abundance of intrxpuhelul mast ulls. Irpochrome deposits and cytoplasmrc PAS stained oagarsciks of urwktcr- mined type in cduted cells ) Terzakis, l. A, Sornn,rrr, S. C. and Audensotb B. liborNory lwrnrlrallon 26(1):127-1)2, 1972. From the (kpartmcot of Patho{ogy, t<noa Hill llospital, New York. THE EMFRGIN(i (]FiNETICS OF RNA TUMOR VIRl1SFS Recent work in the vird fktd has uncovered much informaliao necessary to sct the state for agenctic andysrs of RNA tumor viruses. Conditional kthd mutrants of avian sarcoma viruaca have been isolated and characterized physK>Io2icr,IFy, rarul several types of nonconditional mutants have been de- t+crrbed, the ease with which RNA tumor virus mutants can oe obtaincd suggests that there will noon be eoough of them to allow eshau_tive genetic studies. This edrtorid considcn the likely ramifkralions of RNA tumor virus genetres and formulates speci8c Aypahr~es which are testabk and thus may be proved or refuted. The characteristic features of inheritance among RNA tumor viruses most be diclated by the structural peculiarities of the viral ferwrne, its possible interaction with the cell, and its replication and assembly into progeny vituscs. The •vat genome is probably the 70% RNA estractable (rom purified virrons, though genelic contributions from the 7S component have not been -uicd out. The 70S molecule does not seem to have a contrnuous sugar phosphate backbone but ^ppean to consist of )SS subunits hnkcd to- gcthcr by hyJrotcn bonds. One 70S mokcuk may contain 1-1 tuch subunits this segmemation of the viral gcrso+ne must have important genetic conse- quences and serves as a-ey assumption in the three hypwhcscs presented in this paper. VnIr. r. K. lournat of the Nnnund ( oncrr hurUurr 411(1),3 9, 1972 0l/srr ruplrurt: Nalurnal (lnccr Instilute froro the I~cpArrnrcnr ul MKrohnrlugy• lJaavcrsuy of Suuncern California $ hrM l of A1cJ-ni• 1 irs Angclcs GFNFIlCA1.I.Y STABI E REASSURTaSENT OF MARKERS DUR1NO MIXFU INFf:C{ilON WITN AVIAN TUMOR VIRUSES In this ^vran viral uudy, helper-independent Rout sarcoma virus (RSV) and avian leukosis virus, both characterized by a different hosl range, were allowed to interact durinC mised infection of chick embryo fibroblasls. Several cultures of type CIU chicken embryo fibroblasts were infected at a multiplicity of about I with PR RSV of subgroup A and one of the following kukoais viruses RAV-2 (subgroup B), NT-877 (subgroup C). RAV-7 (subgroup C)• or ('arr 71fber associated virus (CZAV. subgroup D). Alter eight days and thrne lranders at 2-day interv-is the cells were compkrely translormcd, and culture fluids containing high titcrs of virus were harvested. Focus rruays were carried out according to uandard procedures Results of these esperirnents demw- atralcd she presence of pcoseny sarcoma virus with an espanJcd host range as compared to the parenu6 PR RSV-A. Espcriments were designed ^ho to test r progcny of mrsal infections for the preaence of genetically atable viruw w~ich combined the cclt-transforming ability of PR RSV-A with the charac- Ieristic host range of the kukosis virus that had participated in the swiaed infection. The eaperirnents described here indicate that miaed infectiorr with certain pairs of RSV ranC avian kukosis viruses give rise to stable combiwlion forms which carry the host range marker of the lcukosis virus and the Iranra- Iormalion marker if RSV. Formally Ihew agents may be regarded as either avian kukosis viruses which have acquired the ability to transform or as RSV which has eRchanged its bosl range marker for that of a kukoaia virsu. llsr evidence for genetic recombioatiow is promising but still quite preliminary. Yogr, P. K. Viroloty 460) 917-932, )971. . From the Department of Microbiology. Univenity of Washington School of Medreine. Seattle. 111. Cardiovascular System THE RENA1. CIRCULATION This review of renal physiology is mainly conccrned with she Intrarenal distribution of blood fluw, the physiological conseqocnces of changes ira din- tnbution of flow, and the vascsdar anatomy of the -idney. 11+e authors atrer that measurement of total organ blood flow is insuflicient to aascas overall functional stale of the diseased kwlney; distribution of blood flow within the -rdney must ^Iso be dctermined the authors discuss she varqus melhods currently available for the meawremcm of renal blood flow drsrnbution in man, and suRaest that much remains to he esplored in basic renal physiology; and they Jcscrihe the results of renal vascular anaromy studies in Jogs. then apply the general pattern to man in whom it appcars to he srmdar they cwxluJe that the rich adrencrgic and clwlrncrpc innervarrrn Of the renal vessels, and thcrr responsrvcncss to ncurollcnK stimulation. suggest that the aurwwmuc ncrvorn system has an mrlrrrtant role in the rckulauan of flow drstnburasn; humoral factors. however, such as anrKrtcnsin• antuLureuc hormurse, aJrcnal ttcroidt, ^rx! orhers, m.ry Aw be mrpurlaut in rcgularint rmrarenal hkiod itow )) 32

in Ixallh and Arxvx .nJ rncrcatrng knowledge of Ihesc mjy k.J to rmprovcJ therapy uf rrnrl JiutrJcrs Burgrr. A(- arK1 /IcrJ, I A. New 1;nKfunJ bwrn,d u/ MrJrrrnr 284: 4Il?-490, 1971 OtArr .upp..rr: U S Puhlrc Iftallh Service. From the Ikpartmenl of Physiobgy, Har.ard Medkal School, Boston h!'.CRFAtiI l) SYS1OI IC 81 (XN) PRESSURE 111ROt/G11 l)PI.RANf (-ONI)I1IONIN(i 1F('IINI(jUES IN PATIENIS W1111 I-SSfN1IAl- FIYPF R TENSION lhis report describn the use of operant conditioninp feedback techniques to bwtr systolrc blood pres.ure in stve• patients with modcrale or severe hypcrlension, All were .mbula(ory, ssad had an average age of 47 9 yeara. Mtanrngful dccressts in systolic blood pressute, rangtng from 16 14 mm of rnercury, were obtained in five of the palienls- According to the authixs, Mtw. ever, the thcrapculrc valuc of such kchniques still remairo to be established. Benson, 11 , Sy+aprro, I) , Tursly, B. a.d Schw.rtz, O. E. (BnrRcr, A. (-.) Scirrw. 17) ()')9d) 740-742, 1971. Other .rpport: National Institutes of llealth, IloRmann-1A Roche Inc ,nd (Mice of Naval Rtx.rch I rom the Hsrvard Medical 11ni1, Boeton CNy Ilospital, Dcpartmcnl of Mcdi- crne, and Mauachusetts Mental Fleallh ('enter, /larvard Mcdreal School. Boston. CARUTAC OUTPUT At REST IN iFIE SQUIRRF:L MONKEY: R01 E OF P AI)R: NER(i1C ACIIVIIY Receol stuJres have shown that in the squirrel monkey, persistent elevation of mean systemic arterial blood pressure can be induced by schedule-conlrolled behavior and while the cardiovascular mechanisms underlying such hypertension are slill unckar. these inveslijaton fell thal because adrencrgic infl-rences have been implrcated in o(her welltharacteriztd slaln of ekvaled arterial pressure, additional in/ormatwn on the dependence of the normal cardiovascular function of this animal on adrenergic activity would be useful in the characlcritation of behavioral hypcrlension, Consequently. they measured resting carJuc outpul, hlood pressure and heart rate, nd their dependence on fl-adrenergic tone, io the untralneJ, unaneslhelited squirrel nsonkey. lhe resting cardiac output was 319 t 61 (SI)) ml/min, and the resting heart rate was 2A) ± 4) (Sh) twats/ min; treatment with propranolol hydrochloride (201-) 0 mg/kg, im) decrenstd cardiac output and heatl rale, hut not mean systemic arterial pressure. lAe nuarm.l effect of proprarwbl observed aller doscs of 1 0 or ) (1 nrg/kg was a 2S'X. .kcrease in catduc output and heart rate; mcan syslcmtc artctial preysure anJ n.can rrght .uul pressure were rxM changed srgmficantly; cakulatcJ stroke vulumc remnncd conslant, whereas calculated total perqdrer.l re~nlan.e was marleJly incrc..cJ Ihcy cnnclude that 1ladrenerrrc rctivrty pl.rys  malur rolc rn the Jclcrnnnahirn of res/ing urJrac cwtput .rnJ heart rut: in the un. .nr+rhrlurJ tyrrrrcl ni"nkcy 1)rarcn, 1 M, unJ I IcrJ, 1. A. (B,oKrr, A. (- ) Ararrirun luurn,J n/ Phytirdupy 2??1419N8-99), 1972 Oth.r.upp.rrt: (1 S. Puhlk llealth Scrvrcc. hr.Nn the I'.y.hnhiulogy l.ahoraloty and the Ikpar,mcnl of Phystoloty. Flsr• varJ MeJrcal Schuul, Boston. 1Y11? 1'FFI'(°r OF INIIAI AlION OF ('IGARIiI"IE SMOKF. ON VI NIR1('(11 AR 1-11iR11.1 A'1I(IN ll-IRES11l)LI) IN NORMAL IXX;S ANl) IXXiS WI111 ACllll? MY(JCARDIAI. INFAR('l1ON Ihe eRcct of inhalation of cigarette smoke on the ekctzical ventrkular Bhnllation thresholJ (VF1) was studicJ in dwmal JuRs and .krgs with acute myocrtJtal inlarction Two groups of esperiments were pcrformcJ. In the flrM grotr/+, the VV1 was JclcrmmcJ in iwtacl dogs by Jcllvrrrnr ekctrkal wnpulsn through the chest wall. In the seconJ group the imptdus were delivered directly to the hearl through previrsusly implanted eprc+rdial ekclrodes. In Group A the VFf was Jeterntincd in 12 normal dogs at 1S-minute inurvals before, and for a period of 9(1 minutes fter, the nimals h:.J inhakd cigarette smoke O cigarelln, each containing appro.unately 2 mg nico(Ine, in 10 minutes) Similar stuJics were also perforrned in dogs with e.pertmenlal myo- cardul infarction in the acute uaje. Iklermina/ions of VFI' in Gruup B animals were pctformed before and after inhalation of cigarette smoke at IS-minule intervals lor Iwo hours. len corMrol and ten smokmg caperimenls were perlormeJ on nwmal dogs. Results showed a dccrease in VF f that avelagcd 30 to 40% of I/ie conlrol value in normal dors as wcll as in those with acute myocardial infarclion. lhis ellect of inhalatiun of cigarette smuke was evident )0 minules after smoking, became masinmm at about 45 minules, and lasted for about 90 to 120 milutcs. In the dogs with myocardial inlarcuow, the VIT was lower than in nlxmal dogs and was decrcascJ further after inhalation of cigarette smoke. lhese findings are of interest in view of the increaaed incidence of sudden death observed among curunary patients who are heavy cigarette smokers. erflrr, S.,• DcGuzman, N. T., Kostis, 1. B.. Roman. I.. and 1 kischmann, 1). Arnrricon Ilrorr /owrnul 111)(11:67-76, 1972. Other support: Naticxul Inslilutet of Ilcalrh arsJ Amcrican Medical Asw- C/a1Mtn. From the 1)ivaKrn of CarJKrlogy, Philadelphia (:cncral Iluspdal, Philadelphia. I I I I F('f 01' ( I(:ARF:1-II: . SMOKI'. ON 1111: ( ARI)IOVAS( III AI( SYSII M IN D(1(iS A tutal uf Ii Ixvllhy m..li nwn8n'1 JhrCs wa% uu-J rn Ihrs s1uJy u/ the elfect ol inhil.rluon of crgarcllc surwle un Ihe I.crn,4lynjuu, s ol the dux V.rrotn krKrwn ph.rmicolu6rc.rl agcn,s, rK, lyr.6nrn1c. prulrr,rrA,r1. wcrc used 14 35