Journal Article

Metabolic proficiency and benzo[<i>a</i>]pyrene DNA adduct formation in APC<sup>Min</sup> mouse adenomas and uninvolved mucosa

Abid Sattar, Alan Hewer, David H. Phillips and Frederick C. Campbell

in Carcinogenesis

Volume 20, issue 6, pages 1097-1101
Published in print June 1999 | ISSN: 0143-3334
Published online June 1999 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/20.6.1097
Metabolic proficiency and benzo[a]pyrene DNA adduct formation in APCMin mouse adenomas and uninvolved mucosa

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  • Clinical Cytogenetics and Molecular Genetics

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Tumour formation may involve interactions between genetic factors and environmental carcinogens. Adenoma formation in APCMin/+ mice is associated homozygous adenomatous polyposis coli (APC) gene mutation, but the effects on carcinogen susceptibility are unknown. This study tests the hypothesis that APCMin/+ adenoma formation is accompanied by changes in metabolic proficiency and carcinogen susceptibility. Cytochrome P450 (CYP)1A1/1A2, glutathione S-transferase (GST)α, μ and π classes and DNA adduct formation were assayed in adenomas and uninvolved mucosa from APCMin/+ mice, before and after benzo[a]pyrene (B[a]P) treatment. In untreated adenomas and mucosa, CYP1A1/1A2 and B[a]P–DNA adducts were undetected but GSTα, μ and π class enzymes were constitutively expressed. In adenomas, B[a]P only induced CYP1A1/1A2 to low level while GSTα and π class enzymes were unaffected. A GSTμ band which was absent from mucosa, was induced in adenomas. In mucosa, B[a]P induced CYP1A1/1A2 and GSTα and π, to high levels. B[a]P–DNA adduct levels were 56 ± 15/108 nucleotides (median ± SE) in adenomas versus 89 ± 19/108 nucleotides in mucosa (P < 0.0001). APCMin adenomas show reduced bioactivation capacity and sustain less DNA damage from B[a]P exposure, than APCMin uninvolved mucosa. These properties could influence mutagenesis and subsequent neoplastic transformation of adenomas.

Keywords: AhR, aryl hydrocarbon receptor; APC, adenomatous polyposis coli; B[a]P, benzo[a]pyrene; BPDE, benzo[a]pyrene 7,8-diol-9,10-epoxide; CYP, cytochrome P450; FAP, familial adenomatous polyposis; GST, glutathione S-transferase; HNPCC, hereditary nonpolyposis colorectal cancer; Min, multiple intestinal neoplasia; MIS, microsatellite instability.

Journal Article.  4034 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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