Tobacco Documents Online

I . 4x5 card -- to be placed inside front cover . Cospli.ents of The Council for Tobacco Research-U.S.A., Inc. 900 Third Avenue tiew York, NY, 10022 1 CTR cohtTRacTS 025168 11244917 CC1P'JF-.T iF-"-*-'Q._.. CTR HN 043709

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t r October 1, 1984 MEMORANDUM TOs Robert F. Gertenbach CCi wDH scs FROMe Leonard S. Zahn SUSJECT: Press Release for MAI Report Here's•a draft of a press•release on the MAI report. I urge all of you to read it very, very carefully and to give me your views and suggestions as soon as possible. I've tried to avoid judgmental words except at the be- ginning (e.g., massive) where I want to convey the extent of the project. I hope Charlie will look closely at my explanations and "translations" to make sure I've not over-simplified or omitted anything that is significant. There are some appar- ent discrepancies in the MAI summary that he may be able to clarify for me. You'll note I've included several "negative" findings which, in terms of.the major thrust of the study, probably are not important. However, they are'included to show we are not trying to conceal adverse results. I plan to.go over the release with Charlie. I suggest sending the release to Ed Jacob after a con- sensus is reached with you and staff. LSZ I 1 10 75 .n ~ .~. ~,a GasdMoeiataht 13 LINCOLN ROAO •P.0. eOX !!3 •eRLAT NLCKK N.Y.730tZ •p1sKtl4tl! ...... ~ar... . ~....._~.~: . . . . - .. ..-... . CTR CONTRACTS 025162 11244911 22310 CCIP4F-1 C#"N''%,eT 1C FW_ CTR HN 04,37`03

I 4 . eonard alin S CO"NSa Draft -- Oct. 1, 1984 aredAssociatr~lna 13 LINCOLN ROAD •PA. SOX 223 •ONEAT NECK. N.Y.11022 • 1i1i1at2471i FOR: The Council for Tobacco Research-U.S.A. FOR REL$ASE ................................ . ge Inhalation Study Does Not Induce Any Lung Cancer of Type Reported to Be ~ Associated with Smoking by Humans xes ~ . More_ Than'O_,000 Mice Exposed to Smoke PVA Over 800,000 Cigarettes In Largest Project of its 1Cind Ever Chemically Induced Lung Tumors Not Affected by Long-Term Smoke Exposure .` All TYpes of Lu..e Tumors Found Equally In Smoke-Exposed and Unexposed Animals . ME CTR -CChtTRACTS 025163 11244912 22310.01 C'c. i 9''q r. =' x L"# c- , v, IT 11 =~t a_ i ) CTR t-IN 04~~f`"0A,

! 6. . Smoke exposure did not alter the immune status of the ice. ' Prolonged exposure to smoke had no •ffect on the natural loss of,oocytes (egg cells) from the ovary. There have been reports of a relationship between smoking and early onset of menopause (when the ovaries are•depleted of oocytes) . The scientists at Microbiological Associates said in an introduction to their reports "Chronic smoke inhalatioo studies were designed to determine if potential biological effects occur in inbred strains of mice during long term exposure to whole cigarette smoke. In hymans, data to date suggest that cigarette smoke possesses weak bio- logical activity. Becau'ae of,this weak biological potential and because of the conditions under which humans are exposed to cigarette.smoke, it is a necessary requirement that any smoke exposure study uses 1)conditions whereby the smoke deposition and distribution parallel that of human smokers, 2) duration of exposure which parallels that of a human smoker, 3) an animal model which is capable of developing those types of biological lesions associated with cigarette smoking in humans, and 4) a number of animals sufficient to arrive at a significant conclusion." The Council for Tobacco Research is the outgrowth of an organization formed in 1954 by tobacco anufacturers, growers and warehousemen to sponsor research by independent scientists into smoking and health. Itrhas so far provided about $91,000,000 for this program. The Council does not operate any research facility. A Scientific Advisory Board to the Council evaluates applications for research support, judging them solely on the basis of scientific erit and relevance. -END- , CTR CONTRACTS 025167 11244916 +^:C1P%pF-.T DE-J''%1*T.T f=IL._. 1 CTR NN 043roa

New York -- A massive inhalation study in which sore than 10,000 mice were exposed to the smoke from over 800,000 cigaret'tes did not produce a single lung cancer of the type often reported to be associated with smoking by humans. The nine-year study, the largest of its kind ever done, also ? found that mice pretreated with a potent chemical carcinogen ~ did not get significantly inereased lung cancers after long-term smoke exposure. Further, all types of lung tumors identified occurred about equally in the smoke-e~cposed mice, in "sham" ice (treated identically but with~~9,p~°smoke exposure) and in mice literally kept on the shelf as controls. These and other major findings were disclosed in a book issued today by the Council for Tobacco Research, pev York, which funded the 1975-83 study and bad the book -printed. The book, "Chronic Exposure of Mice to Cigarette Smoke," is the complete and unedited final report of scientists at Micro bYological Associates, Inc., a well-known research company in Bethesda, MD, which conducted the study under a contract with the Council. A foreword by Dr. Sheldon C. Sommers, Scientific Director of the Council, said the project "represented a determined effort to develop a suitable animal model involving chronic cigarette smoke exposure of inbred ouse strains known to develop various histopathologic types of 1unE carcinoma afte;1intratracheal administration of pure chemical carcinogens. "It is believed the report will be of.interest to those en- gaged in inhalation research and in the field of investigating human smoking and health relationships," he said. The project required about 11,000 animal-related manipula- tlons daily. The scientists performed autopsies on the animals, ~ microscopic examinations of tissues, data evaluation and re- evaluation, and final analyses of each phase of the study. (MORE) CTR COhtTRACTS 025164 11244913 C:C"M11'14-- I C.X-E=11'41` I f=-'1I(._ C .'"~' HN 0~• ~ ~"`~'.~

. 2. Y~ t~• Ifo The animals used were females ofA:mouse strains that were developed to be genetically susceptible to the induction of lung tumors by various cancer-causing chemicals. Essentially, three major smoke inhalation experiments were done with specially made high tar-low nicotine and high tar- high nicotine cigarettes. Two experiments assessed the carcino- genic potential of cigarette smoke either alone or in combina- tion with a chemical carcinogen given prior to smoke exposure. The third evaluated {.sU~ort-term tests as potential early indica- tors of possible ~e.~i.€ologic effects of exposure to either type of cigarette. There also were corollary studies on the deposition and dis- tribution within the animals of smoke constituenta and selected aerosolixed chemicals. The mice were placed in holders that•. permitted noSe-bnly exposure to s6oke generated- by a machine. Tests showed the mice inhaled at least 90% of the smoke. Among the findings of the study were theses No squamous cell lung cancers, the type reported to be asao- 'j : ciated with smoking, especially by en,. ' „seases.etwere found in the smoke-exposed, sham-treated or shelf control animals. Alveolar adenocarcinomas, a type of cancer reported to be associated with smoking by women, occurred at the same rate in r` both smoke-exposed and sham-treated mice but appeared sooner in ;• the former. (Alveoli are sAd'=11kostructures'ttirough whose walls gas exchange takes place with pulmonary blood vessels.) _Animals developed ixariety of lung lesions,-including aqua- mous celi cancers, when given methylcholantbrene (MCA), a po- tent carcinogen. Daily smoke exposure did not change the types ~\ 1 of tumors compared to sham-treated controle,t.,. 4A The sham-treated micc given MCA had a higher incidence of, and/or a shorter latency for, all alignant lung tumors than '' the MCA-treated mice which were exposed to smoke. . (MORE) CTR CONTRRCT5 025165 11244914 E)[ZJ"`,Jr.1 i=k-.. ) ) ) CTR f IN 0437 0_G_

3. t A comparison of the occurrence of all types of cancers showed a 27% incidence for the smoke-exposed group and a 29% incidence for the sham-treated controls. A higher frequency of one type of cancer, head and neck fibrosarcoma, was seen in the smoke-exposed mice compared to the aham ice. The mechanism for this is unclear. A greater incidence of various tumors of the blood-forming system was seen in the sham-treated controls'(19%) compared to the smoke-exposed animals (13%). The latency period was shorter A lesion reQuently seen in the smoke-exposed animals was accumulation of pigmented alveolar macrophages, which are part of the lung's defense system. Also seen were squamous meta- plasia (stratification) of tracheal cells and rhinitis (nasal tissue inflammation). Assays for short-term ieTTV*A6-V data found that inhibition of cellular DNA repair (deoxyribonucleic acid, which carries gen- etic information) depended on cigarette type and length of amoke exposure. High tar-low nicotine cigarettes bad a greater effect than high tar-bigh nicotine cigarettes during exposure of 30 seconds a minute compared to 15-20 s¢eonds a minute. Both cigarette smoke and certain chemical carcinogens wsre T it-.-~XAfi 9 able to stimulate DNA snythesis, but these effscts did not seem • rl "E ~ ~ ,. to be additive, synergistic or antagonistic. ~~ Smoke exposure did not cause so-called single strand breaks ' in the DNA of pulmonary cells, nor did it influence the level of DNA damage caused by chemical carcinogens. A two-fold induction of pulmonary ornithine decarboxylase, ao ensyme system that may be a possible marker for tumor promo- tion, was seen after daily exposure to smoke for 3 or 6 months. Sister chromatid exchange was induced in bons arrow cells of ice after smoke exposure. The induction was about two-fold and was seen after one week of exposure. Continued exposure for up to 46 weeks showed no further increase in the number of ex- changes. (Chromatids make up a chromosome, which transmits genetic information). (!lORE ) . CTR COh4TRRCT5 025166 11244915 +.ON B1f~= -• ~••I~~ A•'~•d ~" 7r ~F° 1L__. tlV' I IZ I MI I I 0 43  `•M' 7`