Metabolism of phenylhydroquinone by prostaglandin (H) synthase: possible implications in o-phenylphenol carcinogenesis.
Metabolism of phenylhydroquinone by prostaglandin (H) synthase: possible implications in o-phenylphenol carcinogenesis.
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前列腺素 (H) 合酶对苯基氢醌的代谢：邻苯基苯酚致癌的可能影响。
DOI：
10.1093/carcin/12.1.145
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发表时间：
1991
期刊：
影响因子：
4.7
通讯作者：
Smith,MT
中科院分区：
文献类型：
--
作者：
Kolachana,P;Subrahmanyam,VV;Eastmond,DA;Smith,MT
邻苯酚（OPP）及其钠盐正苯基苯甲酸钠（NaOPP）是广谱杀菌剂和抗菌剂。两者都是Fischer 344大鼠的膀胱和肾脏致癌物。OPP通过肝脏中的多功能氧化酶转化为苯基对苯二酚（PHQ）。由于在大鼠膀胱和肾髓质乳头（OPP-和naopp -诱导肿瘤的靶点）中发现了大量的前列腺素(H)合成酶（PGS），我们假设PGS介导的PHQ对苯苯醌（PBQ）的继发性激活可能发生在膀胱和肾脏。我们研究了花生四烯酸和过氧化氢作为辅助因子存在下PGS对PHQ的代谢。这些研究表明，PHQ确实被代谢成与PBQ具有相同光谱和电化学性质的产物。PHQ随时间的消失对PBQ的形成具有化学计量意义。在缺乏酶的情况下，只有不到10%的PHQ转化为PBQ，这表明自氧化在PHQ转化为PBQ的过程中可能只起很小的作用。当用髓过氧化物酶或辣根过氧化物酶和过氧化氢作为辅助因子代替PGS时，得到了类似的结果。这些研究提示PGS将PHQ过氧化代谢为反应性PBQ可能在opp诱导的大鼠膀胱和肾脏癌变中起重要作用。
o-Phenylphenol (OPP) and its sodium salt sodiumorthophenylphenate (NaOPP) are broad spectrum fungicides and antibacterial agents. Both are urinary bladder and renal carcinogens in the Fischer 344 rat. OPP is converted by mixed-function oxidases in the liver to phenylhydroquinone (PHQ). Since appreciable amounts of prostaglandin (H) synthase (PGS) are found in rat bladder and kidney-medullary papilla, the target sites of OPP- and NaOPP-induced tumors, we hypothesized that a secondary PGS-mediated activation of PHQ to phenylbenzoquinone (PBQ) may occur in the bladder and kidney. We have studied the metabolism of PHQ by PGS in the presence of arachidonic acid and hydrogen peroxide as co-factors. These studies showed that PHQ is indeed metabolized to a product having identical spectral and electrochemical properties to PBQ. The disappearance of PHQ with time was stoichiometric to the formation of PBQ. Less than 10% of PHQ was converted to PBQ in the absence of enzyme, indicating that auto-oxidation may play only a minor role in the conversion of PHQ to PBQ. Similar results were obtained when PGS was replaced with either myeloperoxidase or horseradish peroxidase and hydrogen peroxide as co-factor. These studies suggest that the peroxidative metabolism of PHQ by PGS to the reactive PBQ could play an important role in OPP-induced urinary bladder and kidney carcinogenesis in rats.