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Quantification of phase I/II metabolizing enzyme gene expression and polycyclic aromatic hydrocarbon-DNA adduct levels in human prostate.

机译:人前列腺中I / II期代谢酶基因表达和多环芳烃-DNA加合物水平的定量。

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BACKGROUND Studies of migrant populations suggest that dietary and/or environmental factors play a crucial role in the etiology of prostatic adenocarcinoma (CaP). The human prostate consists of the peripheral zone (PZ), transition zone (TZ), and central zone (CZ); CaP occurs most often in the PZ. METHODS To investigate the notion that an underlying differential expression of phase I/II genes, and/or the presence of polycyclic aromatic hydrocarbon (PAH)-DNA adducts might explain the elevated PZ susceptibility, we examined prostate tissues (matched tissue sets consisting of PZ and TZ) from men undergoing radical retropubic prostatectomy for CaP (n = 26) or cystoprostatectomy (n = 1). Quantitative gene expression analysis was employed for cytochrome P450 (CYP) isoforms CYP1A1, CYP1B1, and CYP1A2, as well as N-acetyltransferase 1 and 2 (NAT1 and NAT2) and catechol-O-methyl transferase (COMT). RESULTS CYP1B1, NAT1, and COMT were expressed in all tissue sets; levels of CYP1B1 and NAT1 were consistently higher in the PZ compared to TZ. Immunohistochemistry confirmed the presence of CYP1B1 (nuclear-associated and primarily in basal epithelial cells) and NAT1. Normal tissue from 23 of these aforementioned 27 matched tissue sets was analyzed for PAH-DNA adduct levels using antiserum elicited against DNA modified with r,7t8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydro-benzo[a]pyrene (BPDE). PAH-DNA adduct levels were highest in glandular epithelial cells, but a comparison of PZ and TZ showed no significant differences. CONCLUSION Although expression of activating and/or detoxifying enzymes may be higher in the PZ, PAH-DNA adduct levels appear to be similar in both zones. Therefore, factors other than PAH-DNA adducts may be responsible for promotion of tumor formation in the human prostate.
机译:背景技术移民人口的研究表明,饮食和/或环境因素在前列腺腺癌(CaP)的病因中起着至关重要的作用。人体前列腺由周围区域(PZ),过渡区域(TZ)和中央区域(CZ)组成; CaP最常在PZ中发生。方法为了研究I / II期基因潜在差异表达和/或多环芳烃(PAH)-DNA加合物的存在可能解释PZ易感性升高的观点,我们检查了前列腺组织(由PZ组成的匹配组织集)和TZ)来自接受根治性前列腺耻骨后根除术的CaP(n = 26)或膀胱前列腺切除术(n = 1)。对细胞色素P450(CYP)亚型CYP1A1,CYP1B1和CYP1A2以及N-乙酰基转移酶1和2(NAT1和NAT2)和邻苯二酚-O-甲基转移酶(COMT)进行定量基因表达分析。结果CYP1B1,NAT1和COMT在所有组织中均有表达。 CYP1B1和NAT1在PZ中的水平始终高于TZ。免疫组织化学证实了CYP1B1(与核有关,主要在基底上皮细胞中)和NAT1的存在。使用针对r,7t8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydro--修饰的DNA引发的抗血清,分析了上述27个匹配组织中的23个组织中的正常组织的PAH-DNA加合物水平。苯并[a] py(BPDE)。 PAH-DNA加合物水平在腺上皮细胞中最高,但PZ和TZ的比较显示无显着差异。结论虽然活化酶和/或解毒酶的表达在PZ中可能更高,但是PAH-DNA加合物的水平在两个区域中似乎相似。因此,除PAH-DNA加合物以外的其他因素可能是促进人前列腺肿瘤形成的原因。

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