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Metabolic proficiency and benzo[a]pyrene DNA adduct formation in APC(Min) mouse adenomas and uninvolved mucosa

Lookup NU author(s): Abid Sattar, Professor Frederick Campbell


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Tumour formation may involve interactions between genetic factors and environmental carcinogens. Adenoma formation in APC(Min)/+ mice is associated homozygous adenomatous polyposis coli (APC) gene mutation, but the effects on carcinogen susceptibility are unknown. This study tests the hypothesis that APC(Min)/+ 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 APC(Min)/+ 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 a 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). APC(Min) adenomas show reduced bioactivation capacity and sustain less DNA damage from B[π]P exposure, than APC(Min) uninvolved mucosa. These properties could influence mutagenesis and subsequent neoplastic transformation of adenomas.

Publication metadata

Author(s): Sattar A, Hewer A, Phillips DH, Campbell FC

Publication type: Article

Publication status: Published

Journal: Carcinogenesis

Year: 1999

Volume: 20

Issue: 6

Pages: 1097-1101

Print publication date: 01/01/1999

ISSN (print): 0143-3334

ISSN (electronic): 1460-2180

Publisher: Oxford University Press


DOI: 10.1093/carcin/20.6.1097

PubMed id: 10357794


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