Relation between benzo[a]pyrene-DNA adducts, cell proliferation and p53 expression in tracheal epithelium of hamsters fed a high B-carotene diet

article




Wolterbeek, A.P.M.

Roggeband, R.

Baan, R.A.

Feron, V.J.

Rutten, A.A.J.J.L.
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.
Chemicals/CAS: benzo[a]pyrene, 50-32-8; beta carotene, 7235-40-7; ferric oxide, 1309-37-1, 56449-54-8; retinol, 68-26-8, 82445-97-4; Benzo(a)pyrene, 50-32-8; benzo(a)pyrene-DNA adduct; beta Carotene, 7235-40-7; Carcinogens, Environmental; Carotenoids, 36-88-4; DNA Adducts; Protein p53
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AnimalBenzo(a)pyrenebeta CaroteneCarcinogens, EnvironmentalCarotenoidsCell DivisionDietDNA AdductsDose-Response Relationship, DrugEpithelial CellsEpitheliumGene ExpressionHamstersImmunohistochemistryMaleMesocricetusProtein p53Support, Non-U.S. Gov'tTrachea
TNO Identifier
52139
Repository link
https://resolver.tno.nl/uuid:edef6ad7-f7a9-41b7-a4a1-e50d2f062b47
ISSN
01433334
Source
Carcinogenesis, 16(7), pp. 1617-1622.
Pages
1617-1622
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