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

Epidemiological evidence suggests a link between meat consumption and prost ate cancer. In this study, benign prostatic hyperplasia tissues, obtained b y transurethral resection or radical retropubic prostatectomy from UK-resid ent individuals (n = 18), were examined for CYP1 expression and for their a bility, 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 w ell as mRNA transcripts from CYP1A1 and CYP1B1, The compounds tested for me tabolic activation were 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (Ph IP; 500 mu M, n = 9) and its metabolite N-hydroxy PhIP (20 mu M, n = 8), 2- amino-3-methylimidazo[4,5-f]quinoline (IQ; 500 mu M, n = 6) and benzo[a]pyr ene (B[a]P; 50 mu M, n = 5), After incubation (PFMR medium, 22 h, 37 degree s C), DNA was isolated from tissue fragments and DNA adducts were detected and quantified by P-32-postlabelling analysis. DNA adduct formation was det ected in all samples incubated with PhIP (mean, adducts per 10(8) nucleotid es), N-hydroxy-PhIP (2736/10(8)) or B[a]P (1/10(8)), IQ-DNA adducts were de tected in 5/6 tissues (mean, 1/10(8)). The CYP1 inhibitor alpha-naphthoflav one (10 mu M) reduced B[a]P-DNA adduct formation in tissues from two indivi duals by 96 and 64%, respectively. This pilot study shows that human prosta te tissue can metabolically activate 'cooked meat' carcinogens, a process t hat could contribute to prostate cancer development.