429 



CANCER KISEARCH 



\M.IX N« It. PPL IU-44, Dr«r»bo l«>) 

 C«pvTl|h< mi tty C«MW lUvwrk, Uc 



^'«.V%.V>'^ \ 



Experimental Produaion of Carcinoma with Cigarette Tar* 



EnNMT L. WvNDEH.t EvAIITS A. GraHAM, AND AdELE B. C«0MNGE« 



{D^pcrtmml tf Swf^, M'MJhV"" r'aiV^nty .VA»rf ^ MMteinr. a. torn*. Vc^ nd At />•• vua </ Cliint^ 



Itftitit^ttm «f Ik* Shtui ICi«trv>t ItJtihtt tf Sb Htmarmi Cmtm }m Ctftr i*4 AUut 



t>umim.SmYmk,SY.) 



Th* Ujcrv*iinj fre^u«o<;y of prtin*ry c»nc«r of 

 the luof ia iriAny p*rt« of t}>« world hoj woujed 

 ^At inUTc*! is tKi* cooditioB fttxi bu ftimuUud 

 t acarcb for u explAoatioc. In 10^, ^yrtiu ud 

 Graham (40), OD the bMi* of * diaicftl ulA rUtit- 

 IjcaJ Investix&tion, presented evideoce of • red 

 uviciatioQ b«tw««Q lucg cmicer uA nnokiof, *»• 

 peciaDy of <:igw«tl«. Tbtse d*U h«v< b««B w«U 

 ■ub«taDtiat«d by * Ur^-*cA]e British rtudy by 

 Doll and Hill (d, 10) Doth ftudicj (bow«d tb4t tJ>« 

 ruk of d«veloping ukrxxt of tb« lung uicr«L*ej io 

 direct proporlJov to th« unount of nnoldug. Ten 

 other recent itudies reftched (imiW concKuioox 

 (S, 11, 15, SO, 21, i4, M. SS, M. 4<). In 10£«, The 

 CouAcil of Intemttiond OrganiiAtboJ of )4ediaU 

 Sciescei convened a fyrnpotiuin on the eodemiolo- 

 gy of lung CAOcer tod »gre«d tint tLe present cri- 

 dfoat poiaU to ft rd&tiotohip betireca long cAaccf 

 «nd cigarette UDokbg (It). 



TobA<xo u ik) thought to pUy lome role is tlte 

 production of ctnoer of the Itjyixz, ord ck\'Ay, uid 

 esopbagUB .M'Jiou^h the ftud'>ei of tho6e reULioc- 

 ihip« kt* not 10 complete m th« <tudje< on long 

 csncer, the coQectad d«U we >uggettiv« (SS. 41). 



Hm bci«*<bg uKukaoe d brabduogemc cw- 

 djKtfnA and the •▼uUble evid«&c« reltUog flDok- 

 ing to it aad powbly to cuaoer d other aiteji led at 

 to usdertake the czperusestjJ work reported hei«. 

 Tluj iBv«ati(>ti(» ii ditected toward d«temiiiiii( 

 ia Uboratory aaimilt whether there ftre ~»"''^ 

 gniie fikctot* b eigarette ODoke. 



Mta; Attempt have bcea aud* wHh tobacco 

 product* to bduce caocer* in « variety of experi- 

 mental animak. 71m &nt vaa tvpurled by Broadi 

 IB 1900 (4). Be painted guine* pigs with tobacco 

 "juk«" for an unksowb period of Ume and de- 



* Thii tDTtstjfitjoo »M nf/fetXtA Vy • itaeaieh fnal (ms 

 tW Nuiooal C«nMr lMtJ(«U of tW KttieMl LuUMo ^ 

 BultK ISbUe Beahk Bwrtee. 



t PrcMSl A4)ai«a: M«««rial CeoUr (or C«n«*r ud AllM 

 DiM»Ma, M« Em( SUtj-fifiU SOwi, N«* Yeri II. K.Y. 



K«o«v«d (or p«k6Mti«a Jwnc •, IMS. 



•cribed epithelial proUferatioo Subsequectty, 

 many diflcrtat approacbe* to Um problctn •«« 

 undertaJien with Tariou* tv'pct of tobacco, diS0> 

 ent methodj of tar prrpantiOD, and different i^ 

 ci«s of animali Many of tLoiic aluJies were cftrnad 

 oo for too brief a period of time or with too Irw 

 aQimals to be regarded u sigoi/icftot. Hoffmaea 

 aod hJsuKCJate* (l7),forinstjTKe,painleda(iiiiMli 

 for only 14 dayt, at which tinte they noted ^ix 

 loM. Wacker and Schmincke ()7) observed pr> 

 liferatioa d epilbelium in rabbits' cats %\ dajri 

 after a subcutaaeoai iojectioD of pipe tar. 



The first recorded erprriment with mice aad 

 with tobacco tart aa the luspccted carcinogen vm 

 the ooc juft died by Uoflmana and co- worker*. T\t 

 more detailed o/ t^ (ubaetiuent itudiei are lIjtBrf 

 in Table I. Thii t*bk attempts to fuau&«n«e tkt 

 B>ethoda ued b iJU various itadiet aad tkc i» 

 MiKs obtaiaed. Ik many iastsoce* the method tf 

 study was not deacrTbed In fuflScient detail to gi^ 

 aO tb« In/onnatioa considered esae&tJal. 



From this iurve7 of the Gt/r«faiie it is found 

 that, before our stikiy, aD the previous atlcupts to 

 produce experiBcatAi c«aocr in mice witli tobMs 

 products were meceuf ul ai the prodoctioo «l oa^ 

 •even epiienooM c*noer« of the sfcja. 



ScveraJ iavtstifaton attenptcd to bduce p^ 

 iDODATj tumore ia mice with tobaooo aoohk 

 Loctfij tad eo>wQfien (M) obtabed oeg»tm i»> 

 sohs b tlus maaatr. Cainpbdl ((), sad ««Meia^ 

 E nmb e ig (13). kowtvcr, ebim to h«ve rauad • 

 agnlficaatty kigker pttecatage o( riihanuT 

 adenomas b the cspcnmcntAl thaa b the eeeM 

 group. It is doubtful that luck a fladbg Is btpo^ 

 tant At aay nte. so tar these Betbods have ast 

 induced true facuacliiogcnic csaciooinM. 



The mAJosity ol the iarestigalun wot Ung witk 

 tobacco tars used rmbbHs as the exparimenta) •» 

 tnals (14, tS, tT-St. M). In view ol the fact tk« 

 the preaeot work deals with mice we ihall ooff 

 briefly list aonc ol tbs itudies with rabbiU. Rois 

 reported the production of carcinoooM b rabUl 

 can after painting the can with a distillate d 

 tobacco (tt. 90, St). Sugiura (M), in atteuptbg 



Ui 



