P53 PROTEIN EXPRESSION IS CORRELATED WITH BENZO[ALPHA]PYRENE-DNA ADDUCTS IN CARCINOMA CELL-LINES

p53 inhibits cell cycle progression and DNA damaging cytostatics induc e p53 protein expression, indicating that p53 responds to DNA damage, We have measured benzo[a]pyrene (BP)-induced DNA damage in association with p53 expression. The most relevant DNA adducts for carcinogenesis , benzo[a]pyrene-7,8-diol-9,10-epoxide-DNA adducts, were measured by s ynchronous fluorescence spectrophotometry and p53 immunohistochemistry using polyclonal antibody CM1, which detects both wild-type and mutat ed forms of p53. Activation of BP in A-549 lung carcinoma and MCF-7 br east adenocarcinoma cell lines containing wild-type p53 was followed b y an increase in p53 protein expression, alpha-Naphthoflavone, an inhi bitor of cytochrome P450 (CYP)1A1, decreased both the formation of dio lepoxide metabolites and the p53 response. The cell lines not able to activate BP, A-427 and SK-LU-1 (both human lung carcinomas), SK-MES-1 (human lung squamous carcinoma) and human fibroblasts, did not show an y increase in p53 immunohistochemistry. The OVCAR-3 ovarian adenocarci noma cell line, containing a mutation in exon 7 of p53, and the SK-LU- 1 cell line expressed very high levels of p53 protein before BP treatm ent and no increase in p53 immunohistochemistry was seen. These findin gs indicate that p53 protein is part of the response of the cells to B P-induced DNA damage.