Instituut CIVO-Toxicologie en Voeding TNO
|Source:||Carcinogenesis, 7, 16, 1617-1622|
Environment · Animal · Benzo(a)pyrene · beta Carotene · Carcinogens, Environmental · Carotenoids · Cell Division · Diet · DNA Adducts · Dose-Response Relationship, Drug · Epithelial Cells · Epithelium · Gene Expression · Hamsters · Immunohistochemistry · Male · Mesocricetus · Protein p53 · Support, Non-U.S. Gov't · Trachea
Vitamin A and β-carotene protect against respiratory tract cancer by inhibiting the formation of DNA damage and controlling cellular proliferation and differentiation, Recently, it has been shown that the p53 tumor-suppressor gene plays a crucial role in the etiology of respiratory tract cancer. In the present study, we investigated the relationship between benzo[a]pyrene (B[a]P)-DNA adducts, cell proliferation and p53 expression and the possible effect of β-carotene on such a relationship in tracheal epithelium of hamsters given intratracheal instillations of B[a]P-Fe2O3 particles suspended in saline. DNA-adducts were quantified by the 32P-postlabeling assay, cell proliferation was quantified 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 (BioGenex, Clone BP53-12-1). A clear relationship appeared to exist between the extent of B[a]P-DNA adduct formation, the induction of cell proliferation and the expression of p53 protein in hamster tracheal epithelium. These results suggest that B[a]P induces cell proliferation in hamster tracheal epithelial cells most likely by the induction of mutations in the p53 gene. Furthermore, p-carotene was not found to influence the formation of B[a]P-DNA adducts, which is probably due to the high B[a]P dose. Moreover, β-carotene did not statistically significantly affect cell proliferation and p53-protein expression in hamster tracheal epithelial cells.