Tobacco Documents Online

A. THE COUNCIL FOR TOBACCO RESEARCH-U.S.A., INC. February 20, 1986 TO: Dr. S. C. Sommers FROM: D. H. Ford RE: Site visit with Dr. D. Buchhagea, SUNY Health Science Center at Brooklyn, February 11, 1986. Grant No. 1702R1 (terminal year for a two-year request) entitled "Oncogene Expression in Mouse Lung," for $145,438. HYPOTHESIS Oncogenes are activated by exposure to ethylnitrosurea (ENU) to induce tumors in mouse lung. Her goal is to identify these oncogenes in order to determine the role they play in inducing lung tumors (in mice). If ENU induces the same types of tumor in fetal lung (mice exposed in utero after injection of the mother), she plans to undertake DNA sequence analysis to determine if there are molecular alterations which are responsible for gene activation to induce tumors. RESULTS During the first half year of her program, Dr. Buchhagen has established twenty one ce,ll lines from foci which have appeared in NIH 3T3 monolayer cultures that had been transfected with DNAs from ENU'induced lung tumors. Colonies have been grown on soft agar seeded with cells from the transfection foci-derived cell lines and nude mouse tumors have been developed following inoculation with cells from the soft agar grown colonies. (For further de- tails, see her recent progress report, No. 1.) Thus, she appears to have developed the experimental resource to study activated genes (oncogenes ?) in ENU induced tumors in adult mouse lungs. Studies of oncogene expression in 14, 16 and 18 day old fetal lung,as well as in lung from aging mice, are underway and she hopes will provide convergent information. She further plans to isolate mRNAs from the tumors developing in these animals and sub- sequently create DNA libraries. She also has plans to initiate an immuno- fluorescent study of oncogene related proteins and hopes to determine which genes are active in expression in the development of normal lung tissue and how they may relate to oncogenic activity in tumor development. Further, she has recently initiated studies with human:lung tumor lines derived from the four basic tumor types described in lung. She appears to have plans which may be more ambitious than practically achievable within the year and a half remaining in her program. BUDGET Dr. Buchhagen has requested $145,438 for her terminal year, which in- cludes $28,000 for an ultracentrifuge. Since the new departmental chairman will be obtaining many new pieces of equipment for the department, this expenditure is probably not necessary. When asked what might be a reasonable amount with which to undertake the program she has described, $75,000 appeared sufficient. This too may be inflated.

Site Visit - Grant #1702R1 - Dr. Buchhagen Page 2 COMMENT It is very hard to determine after a discussion with Dr. Buchhagen exactly how much new work has been accomplished since she severed her research relationship with Dr. Kauffman. However, she does appear to have made some progress herself and the program does appear relevant to CTR's interest in cancer. Thus, while I would recommend support for the final year of her two-year program, I would do so only at a much reduced budget. D. H. Ford DHF/s