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"'.1k Hr1o121oa4 . Nlicrobio0ogical Associates 5221 RIVER ROAD e BETHESDA, MARYLAND 20016 TELEPHONE: (301) 654•340D September 14, 1981 Dr. Sheldon C. Sommers Dr. William U. Gardner The Council for Tobacco Research-U.S.A.. Inc. 110 East 59th Street New YorK, NY 10022 Dear Charlie and Bill, As has been our custom in the past, we have summarized thP meeting between CTR and MA on September 10, 1981. Termination The planned termination of Contract 0030 is on schedule. To-date, all personnel except one have been placed in on-going projects at MA. The reduction in facilities from ti8000 square feet to 62000 square feet occurred as of 711/81. The smoking equipTe!:t wa5 transferred to the University of Kentucky in July without mishap. Cigarettes and cigarette smoke condensate and fractions were also shipped to Kentucky during July. An inventory was made of equipment purchased for the CTR contracts during 1974- 1981. The equipment was itemized as to date of purchase and original cost. A sunenarized list was sent to CTR. MA is making arrangements for the captial appropriation request to purchase this equipment as specified under the terms and conditions of the contract. MA would like to conch.de the purchase before November 1, 1981. Manuscripts A list of publications originating from CTR related work at MA from 1971-1981 was recently sent to CTR. The status of 26 recent publications, those in preparation and in progress was presented at Thursday's meeting. It was pointed out that the list does not include write-up of the long term chroniic smoke inhalation study which is now A OIVISION OF ]'gitta$ke1` r 0 + . 0 . . - - 0 -

Dr. Sheldon C. Sonuiters Dr. William U. Gardner September 14, 1981 Page 2 Ht®Q121085 being completed (C-101A). The possiblity of an extension of contract 0030, with no additional funds, was discussed as means of supporting professional staff to finish writing the manuscripts for peer-reviewed journals. The status of contract 0028, the subcontract with Jay Levy con- cerning xenotropic viruses, was discussed and an extension within the present budget was requested ia order to complete the testing of the congenic lines required before the animals could be sent to Jackson Labs. The possibility of sending the animals to Dr.. W. Rowe was also discussed, in which case the animals could remain at MA. Experimental Update C=101A. Chronic Exposure of BC3F1/Cum Mice to 2R1 Cigarette Smoke. The long term chronic 2R1 cigarette smoke inhalation study is termi- nating on schedule. Data were presented which gave the status of the animals (82 alive as of 9/3181, all are expected to die by 11/1/81), the status of histology and the status of the pathology to-date. BMDP statistical packages are now available for in depth analysis of this experiment and data from the previous inhalation study (1-100) is being modeled in preparation for C-101A. To-date, there does not appear to be.any effect of exposure to 2R1 cigarette smoke on the type or time of occu-rence of lung tumors in BC3F1/Cum mice. C-1016. Exposure of DC3F1/Cum Mice to 3A1 and 2R1 Ci9arette Smoke for One Year. Dosimetry The results of a final dosimetry experiment,performed with the SEM II equipment before shipment to Kentucky, were presented. These data indicated the following smoke dose in the three smoke inhalation studies: .n-C S•

Dr. Sheldon C. 5omniers Dr. Nilliam U. Gardner September 14, 1981 Page 3 N, T®012108.6 Experiment Exposure Reeimen Estimated Pulmonary Deposition of Total Particulate Matter (TPM) 1-100 30 sec smoke/30 sec air for 900-1000 ug TPM/day/mouse (2A1 cigarettes) 10 min; 10 min rest; 5 exposures 10% smoke in a.m., 5 exposures in p.m. C-lOlA 20 sec smoke/40 sec air for 125-150 +,g TPM/day/mouse (2R1 cigarettes) 8 min; 8 min rest; 5 exposures 10% smoke per day. ~-lO1B 15 sec smoke/45 sec air for 425-450 ;,g TPM/day/mouse (3A1 and 2R1 126 min per day. cigarettes) 10% smoke These dosimetry experiments were per•formed using the tissue oxidizer to analyze the tissues. The dose in C-lOlA is approximately one-third the estimated dose determined from Oak Ridge using alcoholic-potassium hydroxide to analyze the tissues. Data will be carefully rechecked and Oak Ridge consulted before final conclusions are made. Short-term Endpoints Animals on test in C-101B have been extensively tested for response to smoke exposure using a battery of short-term endpoints over the course• of one year.. These include induction of pulmonary, hepatic, and renz.i aryl hydrocarbon hydroxylase; pulmonary and hepatic ornithine decarboxylase; pulmonary, tracheal, and urinary bladder DNA labeling index; unscheduled and replicative DNA synthesis usir.g organ culture methods; sister chromatid exchange in bone marrow; lung weight/body weight; lung protein and DNA content; and lung hydroxyproline content. All of these assays have served as markers of exposure to smoke, mLny after extremely short exposure periods. Data on all of these will be completed and summarized for the final report to CTR. Conclusions and Next Meetin9 The possibility of CTR sponsoring a monograph or sl:nposium on smoke Inhalation studies was discussed. MA will outline an approach to this concept and present it to CTR by December 1981. The next meeting, at which the conclusions to all of these discussions should be almost completely finalized, wds suggested for December or 0

Dr. Sheldon C. Sommers Dr. William U. Gardner September 14, 1981 Page 4 H T®U121087 January. NA will keep CTR informed and a mutually acceptable date agreed upon. If you have any questions, please do not hesitate to call. Sincerely, Carol J. Henry, Ph.D. Director, Department of Experimental Oncology . f,Q,uk, . I Richard E. Kouri, Ph.D. Scientific Director CJH:REK/ph cc: Mr. W.T. Hoyt Dr. V. Lisanti