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 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 beta-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, beta-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, beta-carotene did not statistically significantly affect cell proliferation and p53-protein expression in hamster tracheal epithelial cells.
Wolterbeek
A P
AP
TNO Nutrition and Food Research Institute, Division of Toxicology, Zeist, The Netherlands.
Roggeband
R
R
Baan
R A
RA
Feron
V J
VJ
Rutten
A A
AA
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism*; D002274:Carcinogens, Environmental / Q000378:metabolism*; D002338:Carotenoids / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D018736:DNA Adducts / Q000378:metabolism*; D004032:Diet; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D007150:Immunohistochemistry; D008297:Male; D008647:Mesocricetus; D014132:Trachea / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics; D019207:beta Carotene
D002274:Carcinogens, Environmental; D018736:DNA Adducts; D016159:Tumor Suppressor Protein p53; C056612:benzo(a)pyrene-DNA adduct; D019207:beta Carotene; D001564:Benzo(a)pyrene; D002338:Carotenoids