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American Health Foundation <Dana Road Valhalla, N. Y. 10595 Tet: (914) 592 - 2600 Amer7cae Health Foundation 137 0 A.enue ofihe Arner:cas Mew York, New York . 70019 ~ Tel: (212) 489 - 8700 OFFICERS AND BOARD OF TRUSTEES David J. Mahoney, Cheirrnan Ceairman and President I+iOrton Simon. Inc. William J: Levitt. Past Chairman Foundbr- Chairman Levi2t a Sons, Inc. Ernst L Wxnder, M.D.. Presldent Eric M. Javits. Secretary Senior Panner Javits a Jav:ts Watner G. Cos>;rove. Jr.. Treasuwer. Vice Presiden:- Directo:' Sh:elda tdoZel aoland, Inc. TR:ISTEES: John J, 5urns. Ph,D. Vice Prrs'2enfior Research Ho!:h..ar..n-La Rcc.ne, Inc. Thomas L. Cnrystie Sen:o• Vice P:esioent Merri:: L.nC" d Co. Ii::... Mrs Ct•er:e: A Dane ^u. nonal_, C:niel r.!sr;a^,:n; ~:rcc:o:, tMew York Ofaae Mcr:nsey d Ccmpany. Ir.c. Ernest 5. Hor.ard, G1.D. Raler,!~hnson Vate 'resiZer,llPuDiiC AftaC'sCoz:+r,er.:ai Telepnone Se-+:ce CorO:. RalD5 Landau: Sc:D: Cnalrr.,3n & Cn1e: E.ecu:ive C°icer Hslco n t.^.;err.adona!. Inc. M:lce;a?L E. f»a:rip JQse2h ~n;,tAie P2r•,nen M,a-il3o'pnins, Ltd;, Jo!~e W. S:mnons Fres•cen: b C^:e' i asa~ .a C".cer N.ncn->vzrwicn ?rod'uc:s. Ir•.c- Mrs. J=_nniferJones Simon Marvlr, S. Traun , pres:cer.i 9!:cr-.,: ;4ale's as f:.,Lrra:son Cha- rna, Lrncocti Nalional Life Insurance Co. AD'A E. R. 2umwatt; Jr., USN(Rat.)', DaviG L. Davies erscubre Vit:e President :or.n 1- We:szur;er• Pn.D. Vitr cresi,cen: for kesaarch.. Dr. Robert B. Seligman Vice President Research and Development Philip Morris USA Research Center P. 0. Box 26583 - Richmond, Va. 23261 Dear Dr. Seligman: Please accept my apologies for the delay in sub- mitting detailed bioassay reports on~ the study of ANT, ANV and BCG. We have now finished tabulating the results of the mouse skin bioassays from the gross observations, as well as Kistopathologic evaluations and Iwould' like to pass these on to you. As you already know,.the reduced tumor response of mouse epidermis to ANV and BCG c'ompared to AItT represents a masterpiece i~n applied research. The fact that there is a.high rate of tumor regression~ and a lot,w rate of conversion to malignant skinn tumors i s : urthzr ev i dence that we are now' deal i ng with weakly tumorigenic agents. Our standard protocol for the macroscopic observation and registration of benign mouse skin tumors requires that a nodule orn the skin must attain a diameter of at leat 1 mr and must be present'Tor 2 weeks before we record th~is growth as a papilloma. Freo,uently, such nodules regress within 8-10.days after their occurrence. However, occasionally regression takes pl ace after thi s 2 1•seek aeri'od and' after the enumera- tion: of a growth as a papil!loma. tUUo12'103e Ot. .~ 0 P2searCh U''lEt, of ; hrr l',rT,=_roC? 1--ileaii': Fi.L;",'',c:aon

` :"NAYLOR DANA I?+IS T i TUTE .` for DISEASE PFtEVEN T 1r.3?i Page Two evaluated. In any case, the relative differences in the activitiesz Thus, you will note differences in the numbers of tumors recorded from macroscopic observations and those that were histologi-rally ot the three test materials are real and significant. Somewhat startling~ is t*he relatively high rate of lung adenomas and adenocarcinomas in this mouse strain. These tumors appear in mice with advanced age with and without treatment. The occurrence of these lung tumors in the long-term tumorigenicity assay on 200 mice each and the tumor promoter assay on 100 mice each does not permit clear delineation of any trends with respect to any known factors in the experiment, although it appears that there may be a real difference in lung tumor rate of mice treated with ANV "tar° vs..those treated with acetone only. We have no explana- tion for this phenomenon at this time and we do not attach major importance to this observation in respect to the tumorigenic activities of the test materials. I discussed this point with Dr. Wynder and he concurs that these should nevertheless be included in our final draft for pu5lication. As soon as I am able to evaluate the histopathology reports on the inhalation studies witK Syrian golden hamsters, I will prepare a final report. Also, we will ask Dr. Steven Stellrran to calculate s~atisticaI significance of the bioassay findings. Please do not hesitate to ask any specifi~c questions on these data. Sincerely yours, Dietrich, Nofznarrr.. `'' DH/ch Enc1sE cc: Dr. E. L. Wynder