Tobacco Documents Online

( $ i Objective 1 Narrative of Approoches 2~ 3. and State Department personnel abroad, should be halted. • f. Establish, support, and promote smoking-withdrawal clinics which vzould be available at little or no cost to persons ~lho wish to stop sr~oking (of, A~erican Cancer Socfety model programs ). Control occupational, industrial and hygienic hazards. a. Experience has shown that control of industrial health hazards can be effective. Rev~ Federal legislation (PLgl-gg6)is nou available which if adequately supported and enforced, ~lll be of great aid in this area. Strin- gent, continuous revie%,J of older standards and require- ments is essential. The principle of substitution idth • less hazardous materials and of reducing exposure through containn;ent and personal protective devices is well under- stood in industry; believer, str~ger action o~ these principles is still needed. b. Limitation of elf-borne pollutants. The consistent finding of an excess of lung cancer in urban, as compared to rural residents, and the Ide~)tiflcation of chemicals known to be carcinogenic in smog residues and polluted air is compatible with a contribution of air pollution to lung cancer• For these reasons legislative restriction Df sources of air pollution should be encouraged. c. Ultraviolet irradiation from sunlight is a known cause of sRin cancer• Federal standards for sunlight protective creams are needed. Include all consumer products lna "Pelaney-type" amendment. a. Food• Potential carcinogens in some foods include normal eonstltuonts {bracken fern, methylene dioxyalkylbenzenes, cycasin); fermentation products; natural contaminaDts (aflatoxlns); ~an-~;:ade contaminants (asbestos fibers, hormones, ~DT); Bnd direct additives (nitrites~ which give rise to nitrosamines). Stringent Federal require- ments for better monitoring of foodstuffs at the level of the producer and processor, and more adequate testing of comstitue~ts is needed, Care F~ust be taken to avoid replacing a ;xell-tosted carcinogenic agent by a poorly tested, possibly more hazardous one, b. Household chemicals, i~cluding aerosol sprays, Ibis large, gro~.dng and inadequately regulated group of pos- • sibly carcinogenic agents needs inclusion in legislation designed to test for and ~liminate possible carcinogens, as such materials represent potential hazards to users (inc. persons in occupations not protected by industrial standards: dry cleaners, Co~ineti¢iaTis, homema~orsl etc.)l On C~ ~VA TI~NAL CANCE~ p£~V 2-3

' C C Objective l l~arrative of Approaches O, ¢. Medication and COSRmtiCS. Many drugs, inc]udlng stilbes- trol, arsenic compounds, griseofulvin, isoniazid, chloramphenicol, and chlorinated anesthetics have been implicated as possible carcinogens: Legislative require- ments for adequate pretesting, usage restrictions, sub- stitutions as indicated, and continuous reexamination of standards is essential. 4. Expand legislative r~guirements for pretesting of products and processes for carcinogenicity before they are introduced to the public. Control reguire~lents might be imposed at the time of app]ication for patents. Develo~and Education. RedLrce the use of tobacco. ~Jhile the educational programs already undertaken tD entourage voiuntary reduction of tobacco use have achieved some success, further imaginative efforts are needed, esgecia~ly directed at preventing young (10=IB year-old nonsmokers) from developlng the habit• To this end, an intensive educational campaign utilizing p~er-group dis- approval of the practice should be promulgated. The use and support of media and persons influential l.~ith the age group should be sought• Since many young men stdrt smoking whi|e in the A~ed Forces, tMe active participation of the U.S. At~ed forces in a counteractive Incentive program should he enlisted. Insurance companies should be encouraged to offer lower rates to nonsmokers (and R~nusers of alcohol); in the i~terest ~f public health such companies should be encouraged not to in- vest in the tobacco Industry, 2, Inform th~ medical profession. Certain, identifiable groups hav~ a higher risk of developing cancer, arid should receive special preventive care, in particular, smokers, alcoholics, individuals with defined associated diseases (ulcerative c61itis, xerode~]a pigmentosum, pernicious anemia, etc.), the obese, and uncircumcised males• b. Extend warnings about the hazards of certain therapeutic and diagnostic drugs and procedures vHtb the aim Df limit- ing the exposure from diagnostic and therapeutic x-ray (e.g., improved equipment) and potentially carcinogenic drugs such as griseofulvin. c; Establish educat;onal ~.Iorgshops and clinics to inform the obstetrical profession about the great vulnerability of the fetus to r~diation, drug%, and ho~1on{~s adL~llnistered to the mother and the tragedy of prenatally caused cancer, Through these programs, children l,ho have already experienced preilatal exposure may be identified for follow-up preven- tive care. A nation~;ide effort should be made to enlist NATIONAL CAN~R PLA~/ 2-4

,.J f t' Objective 1 Narrative of Approaches She proFPssion in preventing penile cancer through circumci~ioR of nov:born males. 3. Infom Occupational Groups. a. Inform and encourage manage~lent tO reduce the exposure of .employees and the public to carcinogenic agents. Explana- tion of the scientific and economic basis for legislative • controls, and the responsibilities and benefits these impose, ~hould be provided. b. Inform labor, through their unions, of self-protective practices, lhese group~ should be warled of the cocarci- nogenicity of combined environmental factors ~.9. additive effect of smoking for a worker in the asbestos industry . c, Infon~ farmers regarding safer use of agri-chemicals and aerosols, a~id the hazard of excessive sunlight, Create a~aremes~ of farmer's strategic po~itio~ in preventing release of environmental carcinogenic agents into air, water and food. 4, Inform Congress dnd the general public. The value of pre- Ventive measures and the d~ngers of uncontrolled dissemination of carcinogenic agents through the envirom~ent urge the main- ten,nee of an ongoing program designed to inform Congress and the public about actual ilazards, tile need for and natul'e of pro- posea and presert legislation, t~e findings of researcrh and the identification of conditions B00 factors reducing ano lncreaslng %he likelihood of developH~g cancer. C~ Ca ~IATIONAL CANCE[f pLAN -- 2~5

( Objective I Rarrative of Approache% .i B, Approach 2+ The Immediate ~!pllcatimn of Technology to Prevention of Cancerin Hu1~lans: ~ment of ~Pications~ ~l vet an~67~ ?or ~-~i- C~rc~ A Not all of the known or suspected carcinogens in the environ~:ent can be ~liminated by the prpgrams described In Approach 1, For some, control Is i~9ossihle~ for others, control methods are at present un- available; for some, son:e control methods are inadequate or present great social or economic cost• For these problems, the aid of engi- neering, chemical, and pharmaceutical industries should be enlisted to devise control devices or substitutes for hazardous processes and products. I. Less hazardous cigarettes and other smoking products• Significant progress has been made already in altering and trapping the oxidation products of cigarettes and rendering them safer. ContimJed intensive efforts in this direction, based upon sound analytical and bioassay procedures {see Approach 3) should be sought. ~. Less hazardous industrial processes and products. '-" The operations of the petrochemical iadustrles, dye industries, and mining (esp. radioactive) industries present special hazards to workers and nearby r~sidents. Employees must be Safeguarded by protective devices and procedures. Ubenever practicabl~, the development of alternatives and substitutes should be encouraged through tax incentives. 3, Less hazardous usage of fossil fuels and alternate energy sources, a. Efforts to limit air-borne pollutants probably can best be carried out in cooperation with those ~ork- ing outside of the area of cancer research. The foll~ving pertinent problems were identified by th~ 1971 Committee on Biological Effects on Atmospheric Pollutants Divlsion of Medical Sciences, t{ational Research Council of the National Academy of Science pg xxix, {I) "Close scrutiny should be directed to deterioration effects of aut~mobil~ control devices and the use of diesel-fueled vehicles under overloaded conditions. C#) Research into the effects of fuel COaTpOSl- tions and of advanced emission control ~OVJC~S should b~ cD~tiDuDd, Polycyclic organic matter emi~slons from aircraft should be assessed, (B) (a) gV C~ G1 -6 NA TIO~VA {. CANCER pLA~

( ( j , q _._~ective I Harrative of Approaches 4, 5. r~ (41 SuhstltuCion of ~Iternate fuels or more efficient co~bustio~) processes a~d discon- tinuance of codl-refuse stora9e practices seeln to be appropriate m~thods for the resLriction of coal~regulated polycyclic orgatdc matter emissions, (5) Emiss{on associated with coke production requires additiondl research on control procedures and source analysis." b. Explore the desirability of substituting alternate ener!]y sources (~*ater, solar, nuclear) for fossil fuels. Encourage the inventim~, production, a~d ma~s m~rketing of highly-protective, Iono-lasting creams to protect the skin egalns~ exposure ~o sunlight, Enlist aid of ~harmaceutical industry In keeplng recor~ and follow-up studies regarding any n~w medication (open records Of doclors {~Ingj atld DaCients receiving, such medication ~o be maoe available ~f needed), ~ZA ~'/Otj~l. C~CER F= A IV 2-7 Oh C~

( i , Objective 1 Narrative of Approaches 3, Approach 3, Detectlon and 14entification of External Cardnoqenic Epidemioloqical studies, particularly with migrant groups indicate thRt several important human cancers have significant ~nvironmental factors in their etiology• Environmental chemicals, both man-made and of natucal occurrence, al-e principal suspects among tdese. Already a number of diverse organic and inorganic chemical car- cinogens fnr the bu~2an have been identified. Zpidemiolocical grounds indicate that additional important environmental chemicals exist that play a determinin~ role in the etio]opy of important bunyan cancers of high incidence, such as cancers of the lungs, colon, stomach, and breast, lhere is a]so reason to suspect that several environment factors, not carcinogenic in themselves may act in con- cert tQ produce human cancers, The likelihood that viruses also contribute to the etiology of human cancers merits continued investi- gation. The detection and identification of any such agent will facilitate rational approaches to YtS elimlnatlon or reduction in the human environment. A major and sustained effort over •several decades {~he 15 to 25 year latent period for development of human cancers requires this time Scale) by epidemiologists, clinicians, add ]aboratory workers in viral and chemical carcinoQenesls will be required. Simultaneously, improved analytical methods and assays should be developed to test the hypothese~ engendered by the epidemio- logical studies• The detection and identification in the environment of agents carcinogenic for humans is of prime importance to the goal of preventing human cancers• A. Zpi~emiological Studies. |.. Establish teams :o~prised of foreign-based and {].S. epidemiologigts, clinicians, and laboratory investigators• of chemical a~d viral carcinogenesis. These te~m effor~, supported by long-term comn)itments of adequate funds and persDn~el, should be directed t~ard comparative studies of the incidence of cance~ an~ understanding of the as- sociated etiologic parameters. The importance of encourag- ing and devising means for maximal cooperation.and exchange of information ~vitMn the team is of the greatest impor- tance. New personnel and training programs will probably be needed. ~. Cigarette smoking. Investigate the effect of modified ~obacco products and smohlng flahits on the incidence of l~ng cancer• Follo,~ the recommendations for reseal-ch by the Cor~ittee on Rio~ogical Effect~ of Atmospheric Pollu- tants Division of Kedical Sciences, National Research £oul)cil of the l~atio~a] Academy of Science (1971}. "Much 9renter documentation of cigaTette smoking is badly needed, lhe exclusion of this major etiologic fa~tor in disease from the 1970 census is unfortunate• Valid esti- mates of cigarette consumption in major community areas, both urban and rural, in relation to lung cancer and other major disease entities are not easily available .... " .. (pg xxxlv.) ~#A~IONAL'~A?ICERp~.AM • Z-8 GI "4

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4 Objective 1 ~ [laG,ive of Approaches I B. A hypotDetical "exposure-experience" profile derived from multifactorial analysis might specify sex, age, weight, mdrit~] status~ therapy regimes, nutritional patterns~ and residence experience. If the 2G-year tumor incidence of a large number of persons matcbing such a profile could De compared Ivith GrOUpS differing in single areas of the profile, some better insight into the complex causes of cancer in humans might be "'Gained. , 6. Study the occurrence of cancer in occupational Groups. 7. Conduct epideniological studies usinG congenital malfor- mations as a concordant for cancer. 8. Hormones (inc. hormonal oral contraceptives) These sub- stances need study in regard to incidence of breast, cervical and prostate cancer on a v$orld-tvide basis. 9. Diet. Further epidemioloGical studies in ~onnection with laboratory investigations are needed on nutritional pattelms and cancer incidence. lO. Drugs. Patterns of cancer incidence and drug therapies ~rit expanded study. 11. lo~-level radiation and its relationship to human cancer incidence needs intense, world-v#ide, comparative study. beve]o~ and Improve Bioassa~s for Carcinohens Relevant to HunI~IIS, Present bioassays for viral and chemical carcinogens and suspected carcinoGenS ar~ inadequate in many respects. Re- producibility, sensitivity, and speed of assay period need to be increased (see IDa8 report of the Discussion Group on Chemical Carcinogenesis of the l~ational Advisory Cancer Council, Appendix I page 20). In particLJlar, reIevanc~ of in vitr~ bioassays to human carcinogenesis must constantly ~e-sought und improved: the criteria of neoplastic change, accessibility of the carcinogen, and its conversion to an active fern, present important difficulties to be overcone. The follD~vin9 five syste~Ls offer promise for bioassays, 1. Host-B~diated assay systems. lhese relatively rapid assays for mutRgenicity and cell C/~ transformation in vitro $~ou]d employ both hm;;an and test . animal tissues to effect the metaholic conversion of the ~w~ chemicals under test to active forms ~hich have mutagenic C,~ or transforming activity in I110 test cell. Host-mea~ate~ assays may leID to reveal False ~ositive and false nega- ~ tire results am~n~ the resu)~s of the ~hole aniF~al Loses NA TfONAL C~4NCER PI.AA .2-I0

( Objective 1 C ~arrative of Approaches e=J for carcinogenirity, and provide priorities for life- ti~le testing of suspected CdrCino~e~s. Transfomation in cell cultures, induced by chemical as well as viral test substalces, should be explored fur- ther• Succes~ in such a syste~ may depend in part on improvement of culture teclmiques aired at d) 9rovting ~ormal an~ prir~y cells on ~ large scale, ~nd b) gr~- ing populations fron single~ isolated cells (cloning). Detection of cell-surface antigens. Cell tran~form~tion by viruses in experimental cell cul- tures is accompanied by induction of surface antigens• These antigens, which are labile dnd complex~ as yet are inadequately characterized. Nevertbeless, quantitative and qualitative analysis of Such cell surface antigens may provide a useful assBy method, as well as providing a method fo- d~tecting ~iral invol~e~ent i~ huma~ can- eers (see D, 2}. Detecting viral activity through specific biochemical characterization of tumor cells. a. lransfonnation of cells by oncogenic R~A vir.ses In- volves the induction of new enzymes, particularly reverse transcriptase. An assay system evincing viral infectiQn could be based upon the detection of such enzymes in the human tissues or in cell cul- tures. If it is learned that reverse tra~scriptase is virus-specific, the enzyme might serve to ideRt- ify viruses in human tisst~es, eve~ in the abse~c~ of virus particles (section D, 2}. b. Dotectino cell messenger RNA complementary to tile DNA product of viral reverse transcriptase by hy- bridization migbt serve as a method of determining vir~l etialogy in human tumor tissue and as' evidence of transfon;~ation in bioassay systems (see D, 2). h~rov~d a~4 additional lo~g-te~m, ~h~le anim~l assay. ~b~se p~oced~r~s n~ ~o~sish of life-tim~ tests of high levels of chemicals administered by various routes to short-lived m~T~als, beuAte their relatively high cost and other deficiencies, these tests are required until . C2~ reliable, rdpid, bro:d spectrum tesPs for carcinogenic- Ity tests in whole animals sbould be unde~.Iritten for • the entire survival period. In the past, valuable data was often lost when animals were hilled because of economic Bnd Space considzrations. Centralized animal ~ maintenance colonies might be considered for this pur- ~,~ pose ~l . ,, . . 2. 3. 4. NA "[#ONA h CANC£R {~LA@ -- 2-11

( Objective 1 Harrative of Approaches C, g, Devise and ~)rove Anir'al Hodels of Hurrah Cancer In&Jcible yb~emica], Viral and Radiation CarciTloqens and Cotrbina- tions "[hereof. For too fe~t human cancers do we have adequate animal models. IChile animal models using chemical carcinogens exist for leukemia and cancer of the breast, liver, colon, bladder, esophagus and lung, most of these are deficient in some regards and need improvement. Even more critical is the absence of any aMmal model for tuN'ors of the stomach, pancreas, and uterus• Animal models are ~eeded for screen- ing for human carcinogens, for studies of factors that could alter the incidence of specific human cancers, and in the basic goal of understanding and eradicating the causes of human cancers, lhe uses of good model systems can be il- lustrated by the studies of skin carcinogenesis in the mouse, where considerable progress has been made in under- standing tbe Stages and mechanisms of carcinogenesis. Models for other organ systems in which staging and modifying factors in carclnogenicity can be studied are greatly needed. Improved Methods for Analysis of Chemical and Viral Carcinogenic Aqents, 1. Better analytic procedures for carcinogenic agents in the environment and in human tissues are needed be pro- vide measures of total exposure to potential human carcinogens• Requirements for a "carcinogen free" or minimally carcinogenic environment (Approach I, 2) must rely ugon rapid, sensiLive monitoring and surveil- lance techniques. The success of epidomiologic studies also must rest on actual measures of the environmental exposure encountered by groups under exanffnation. Improved analytical methods for detection of the carcin- ogenic agents in the host tissues and body fluids are needed for studies directed toward interference with the host-carcinogen interaction• The specific proce- dures most needed will depend upon the demands of the projects undertaken to accomplish Approaches l, 2, and 4. 2. Isolation and identification of candidate viruses, sub- viral particles, and virus-specific antigens in human tumor tissue. A cooperative, wide-ranging program between clinicians • and virMagists should be undertaken to screen many types of human tumors for presence of viral particles. Adequate supporting bioassays and suitable controls will be needed. In addition to studies directed toward C,~ leuhemias, lymphornas ~ aild sarcomas, greater efforts should be made l~lth epithelial tissue and carcinomas. Some of the bioassay apDroaches described in sec- tion Ill, C have relevance as methods for identifica£ion of viFuses, NATtOIVAL CANCER PLA(¢ -- 2-12