Journal Article

Metabolic activation of carcinogens and expression of various cytochromes P450 in human prostate tissue

J.A. Williams, F.L. Martin, G.H. Muir, A. Hewer, P.L. Grover and D.H. Phillips

in Carcinogenesis

Volume 21, issue 9, pages 1683-1689
Published in print September 2000 | ISSN: 0143-3334
Published online September 2000 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/21.9.1683
Metabolic activation of carcinogens and expression of various cytochromes P450 in human prostate tissue

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Epidemiological evidence suggests a link between meat consumption and prostate cancer. In this study, benign prostatic hyperplasia tissues, obtained by transurethral resection or radical retropubic prostatectomy from UK-resident individuals (n = 18), were examined for CYP1 expression and for their ability, in short-term organ culture, to metabolically activate carcinogens found in cooked meat. Semi-quantitative RT–PCR analysis of CYP1 expression detected CYP1A2 mRNA transcripts in the prostates of four individuals, as well as mRNA transcripts from CYP1A1 and CYP1B1. The compounds tested for metabolic activation were 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP; 500 μM, n = 9) and its metabolite N-hydroxy PhIP (20 μM, n = 8), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ; 500 μM, n = 6) and benzo[a]pyrene (B[a]P; 50 μM, n = 5). After incubation (PFMR medium, 22 h, 37°C), DNA was isolated from tissue fragments and DNA adducts were detected and quantified by 32P-postlabelling analysis. DNA adduct formation was detected in all samples incubated with PhIP (mean, adducts per 108 nucleotides), N-hydroxy-PhIP (2736/108) or B[a]P (1/108). IQ–DNA adducts were detected in 5/6 tissues (mean, 1/108). The CYP1 inhibitor α-naphthoflavone (10 μM) reduced B[a]P–DNA adduct formation in tissues from two individuals by 96 and 64%, respectively. This pilot study shows that human prostate tissue can metabolically activate `cooked meat' carcinogens, a process that could contribute to prostate cancer development.

Keywords: B[a]P, benzo[a]pyrene; BPDE, benzo[a]pyrene diol-epoxide; BPH, benign prostatic hyperplasia; CYP, cytochrome P450; IQ, 2-amino-3-methylimidazo[4,5-f]quinoline; NAT, N-acetyltransferase; PhIP, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine; PAH, polycyclic aromatic hydrocarbon; SULT, sulfotransferase.

Journal Article.  5532 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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