TPA DECREASES THE P53 RESPONSE TO BENZO[A]PYRENE-DNA ADDUCTS IN-VIVO IN MOUSE SKIN

TPA, a well-known tumor promoter, decreased the response of nuclear p5 3 immunoreactivity to benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE)-DNA adducts in C57BL/6 mouse skin in vivo. A dose-dependent increase in bo th the level of BPDE-DNA adducts and nuclear p53 immunoreactivity was found in mice treated topically with 50-750 mu g benzo[a]pyrene. Such a positive correlation between the adducts and p53 positivity was sugg ested by an earlier study. Since p53 probably functions in DNA damage control, interference by TPA with the p53 response could be a mechanis m in TPA-induced tumor promotion. Whether such a mechanism is more gen eral in tumor promotion deserves further study.