CELL-PROLIFERATION AND NUCLEAR ABNORMALITIES ARE INCREASED AND APOPTOSIS IS DECREASED IN THE EPIDERMIS OF THE P53 NULL MOUSE AFTER TOPICAL APPLICATION OF BENZO[A]PYRENE

Cell proliferation and cell death in mouse epidermis are altered by to pical application of benzo[a]pyrene (BaP), a procarcinogen, which yiel ds metabolites that can form DNA adducts. The mitotic rate, nuclear ab normalities, labelling index, grain density, necrosis and apoptosis we re compared in the epidermis of TSG-p53 null (p53(-/-)) and C57BL wild -type (wt) mice after weekly treatments with BaP to determine whether the absence of the p53 gene altered cytokinetic responses to DNA damag ing agents in vivo. Acetone alone or 64 mu g BaP in 50 mu l acetone wa s applied to the clipped dorsum of mice once, or in four consecutive w eekly treatments. Indices of cell proliferation and cell death were th e same in both wt and p53(-/-) mice treated only with acetone, One app lication of BaP depressed mitosis and slowed the rate of DNA synthesis in both genotypes. After four applications of BaP the number of kerat inocytes in S phase increased substantially, while there was no furthe r slowing in the rate of S phase in the wt and p53(-/-) mice. Cell pro liferation rates and numbers of cells with nuclear abnormalities were higher and there were fewer apoptotic cells and apoptotic bodies in th e p53(-/-) mice than in the wt mice. Numbers of 'sunburn' cells were s imilar in both types.