Effect of the route of benzo[a]pyrene administration on sister chromatid exchange and DNA binding in bone marrow of mice differing with respect to cytochrome P450 1A1 induction

doi:10.1016/S0378-4274(97)00024-6

Toxicology Letters

Volume 91, Issue 3, 16 May 1997, Pages 211-217

https://doi.org/10.1016/S0378-4274(97)00024-6 Get rights and content

Abstract

The effects of the route of benzo[a]pyrene administration on sister chromatid exchange (SCE) and B[a]P diol epoxide (B[a]PDE)-DNA adducts formation in bone marrow cells of Ah responsive (C57BL/6; B6) and Ah non-responsive (DBA/2; D2) mice were determined. Animals were treated intraperitoneally (i.p.), intragastrically (i.g.) or topically with two 100 mg/kg doses of benzo[a]pyrene 24 h apart and killed 96 h after the first treatment. Significant increase in the frequencies of SCE and the level of B[a]PDE-DNA adducts as measured by synchronous fluorescence spectrophotometry were detected in D2 mice as compared to B6 mice. The route of administration had little effect on SCE levels in bone marrow cells in D2 mice. In B6 mice higher levels of SCE were observed following i.p. administration as compared to i.g. or topical administration. In both strains the highest level of B[a]PDE-DNA adducts was formed after i.p. administration of B[a]P. We conclude that the i.p. route of B[a]P administration is the most effective in inducing SCE and B[a]P-DNA adducts formation. SCE induction does not correlate linearly with the amount of B[a]PDE-DNA adducts formed in these cells after administration of the above dose of B[a]P.

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These enzymes metabolize many of their substrates to more soluble and excretable products, but also as the classic example of benzo[a]pyrene shows, are responsible for their activation to ultimate carcinogenic metabolites. This leads to DNA adducts formation, induction of sister chromatid exchanges and carcinogenesis (Brauze et al., 1991; Brauze et al., 1997; Nebert, 1989; Pelkonen and Nebert, 1982). AhR resides in the cytoplasm as a complex with chaperone proteins: HSP90, XAP2 and p23 (Petrulis and Perdew, 2002).
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Research articleEffect of the route of benzo[a]pyrene administration on sister chromatid exchange and DNA binding in bone marrow of mice differing with respect to cytochrome P450 1A1 induction

Abstract

Mutat. Res.

Toxicol. Appl. Pharmacol.

Arch. Biochem. Biophys.

Trends Pharmacol. Sci.

Mutat. Res.

Mutat. Res.

Relationships between benzo[a]pyrene-DNA adduct levels and genotoxic effects in mammalian cells

Cancer Res.

Formation and persistence of benzo[a]pyrene-DNA adducts in different tissues of C57BL/10 and DBA/2 mice

Carcinogenesis

Induction of microsomal enzymes by foreign chemicals and carcinogenesis by polycyclic aromatic hydrocarbons: G.H.A

Clowes memorial lecture. Cancer Res.

Cultured mouse embryos metabolize benzo[a]pyrene during early gestation: genetic differences detectable by sister chromatid exchange

Ah receptor in mice genetically ‘nonresponsive’ for cytochrome P4501A1 induction: cytosolic Ah receptor, transformation to the nuclear binding state, and induction of aryl hydrocarbon hydroxylase by halogenated and nonhalogenated aromatic hydrocarbons in embryonic tissues and cells

Mol. Pharmacol.

Research article
Effect of the route of benzo[a]pyrene administration on sister chromatid exchange and DNA binding in bone marrow of mice differing with respect to cytochrome P450 1A1 induction