Tobacco Documents Online

Mir•. CoUNCtL FuR ToBACCO RrNLARrir-ii.ti.A.. INC. February 25, 1981 MEMORANDUM TO: Drs. Gardner and Staff FROM: D. R. Ford HKP,4116707p SUBJECT: Site Visist with Dr. R. M. Hoffman, University of California School of Medicine, San Diego - February 18, 1981 Grant No. 1348 "Methionine Dependence, Methylation and Oncogenic Transformaticn" Dr. Boffnan was out of town when Dr. Lisanti and I made our site visit last summer. At that time we met with his colleague, Dr. S. Jacobsen. Dr. Hoff- man impresses one by his enthusiasm and intensity as well as by his competence for the particular study he is undertaking. His working hypothesis is that S- adenosylhomocysteine (SAS) levels are raised in cancer cells and that this causes an altered DNA metbylation, which in turn may be the central event in effecting transformation. Will be measuring S-adenosylmethionine (SAM) and SAN in normal and transformed cells and anticipates that the SAM/SAH ratio will be altered in cancer cells. This ratio, or methylation index may then be useful at some time in the future to determine degree of risk for developing cancer in the general population. Will also determine how methylation is effected by tobacco conden- sates (to what degree is the methylation of DNA in NIH3T3 cells activated by tobacco condensates. Dr. Hoffnan's initial grant provided funds for purchase of a liquid scintillation counter. Since obtaining the grant, he has been able to obtain the use of a counter within the department. He subsequently has used the funds to purchase an HPLC system, which Dr. Jacobs•.n, has already set up and used to develop clear separations of standard samples of SAM and SAH. The next phase will be to accomplish the same degree of separation on extractions from tissue samples. Some of the cells to be tested include cells obtained f rom Dr. Jerry Cooper which have highly oncogenic DNA. Plans to isolate the DNA and determine the effect of in it,;:,o methylation on oncogenicity. Also plans to clone and purify oncogenes in order to study how they may be activated or repressed. New Personnel: Dennis Coalson... a studeut technician who will be going to Medi- cal School rhis fall. Dr. Edward Diala...working on the project, but paid by the Medical School. May become a Research Assohiate in future. Future plans: Once studies with the methylation index in normal and transformed cells are completed, plans to consider effect of gender, age and duration of smoking in a human population. Once normal patterns of distribution of DNA methylation, as determined by the methylation index are completed, would plan to determine if the index has any predictive value as a measure for whether an individual is at risk for the development of cancer. I Observations: Considerable progress appears to have been made in the short time since this grant was activated. While their initial program did not appear too relevant to the goals of CTR, their current thinking in relation to use of smoke con- densates in inducing transformation in relation to the methylation index and future plans to study the effect s of smoking appear quite relevant. Seems like a potentiall5 valuable contribution. D. H. FORD