RELATION BETWEEN BENZO[A]PYRENE-DNA ADDUCTS, CELL-PROLIFERATION AND P53 EXPRESSION IN TRACHEAL EPITHELIUM OF HAMSTERS FED A HIGH BETA-CAROTENE DIET

Vitamin A and beta-carotene protect against respiratory tract cancer b y inhibiting the formation of DNA damage and controlling cellular prol iferation and differentiation. Recently, it has been shown that the p5 3 tumor-suppressor gene plays a crucial role in the etiology of respir atory tract cancer. In the present study, we investigated the relation ship between benzo[a]pyrene (B[a]P)-DNA adducts, cell proliferation an d p53 expression and the possible effect of beta-carotene on such a re lationship in tracheal epithelium of hamsters given intratracheal inst illations of B[a]P-Fe2O3 particles suspended in saline. DNA-adducts we re quantified by the P-32-postlabeling assay, cell proliferation was q uantified by immunocytochemical detection of incorporated BrdU during S-phase, and p53 protein was detected by immunohistochemistry with an antibody that recognized both the wild-type and the mutated protein (B ioGenex, Clone BP53-12-1). A clear relationship appeared to exist betw een the extent of B[a]P-DNA adduct formation, the induction of cell pr oliferation and the expression of p53 protein in hamster tracheal epit helium. These results suggest that B[a]P induces cell proliferation in hamster tracheal epithelial cells most likely by the induction of mut ations in the p53 gene. Furthermore, beta-carotene was not found to in fluence the formation of B[a]P-DNA adducts, which is probably due to t he high B[a]P dose. Moreover, beta-carotene did not statistically sign ificantly affect cell proliferation and p53-protein expression in hams ter tracheal epithelial cells.