Variations in catechol O-methyltransferase activity in rodent tissues: possible role in estrogen carcinogenicity.
Variations in catechol O-methyltransferase activity in rodent tissues: possible role in estrogen carcinogenicity.
复制标题
啮齿动物组织中儿茶酚 O-甲基转移酶活性的变化：雌激素致癌性的可能作用。
DOI：
10.1093/carcin/10.1.63
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发表时间：
1989
期刊：
影响因子：
4.7
通讯作者：
Li,JJ
中科院分区：
文献类型：
--
作者：
Li,SA;Purdy,RH;Li,JJ
儿茶酚-O-甲基转移酶（COMT）[EC 2.1.1.6]是一种普遍存在的细胞溶质酶，在哺乳动物组织中天然和合成儿茶酚雌激素的失活中具有相关作用。我们比较了小鼠，仓鼠和大鼠的肾脏，肝脏和红细胞中的COMT活性，并研究了后两个物种中使用各种儿茶酚雌激素作为底物的这种酶的动力学特征。本文提供的结果表明，大鼠和小鼠肾脏与肝脏中COMT活性的比值几乎相同，为0.48-0.52，而仓鼠这两种组织中COMT活性水平的比值为29倍。在红细胞中，仓鼠的COMT活性水平分别比小鼠和大鼠低4倍和12倍。当在仓鼠和大鼠肾和肝中测定这种酶的动力学特性时，除2-羟基雌酚的Km值为15-48 μM外，其它儿茶酚雌激素底物的Km值范围为1-10 μM。通常，大鼠肾脏和肝脏中的Vmax值明显高于相应仓鼠组织中观察到的值。仓鼠肝脏和红细胞中COMT活性显著降低表明，在高剂量的慢性雌激素治疗下，这些组织中儿茶酚雌激素的浓度可能超过COMT有效催化其O-甲基化转化为无活性代谢物的能力。由此产生的儿茶酚雌激素蓄积可能导致在仓鼠肝脏和肾脏中观察到的雌激素致癌性。此外，当2-羟基雌酮作为底物时，雌激素诱导的肾癌仅表现出正常肾脏中发现的COMT活性的8.6%。
Catechol-O-methyltransferase (COMT) [EC 2.1.1.6] is a ubiquitous cytosolic enzyme which has a pertinent role in the inactivation of both natural and synthetic catechol estrogens in mammalian tissues. We have compared the COMT activity in mouse, hamster and rat kidney, liver and red blood cells and examined the kinetic characteristics of this enzyme in the latter two species using various catechol estrogens as substrates. Results presented here indicate that the ratios of COMT activity in the kidney versus the liver of the rat and mouse are nearly identical, 0.48–0.52, whereas there is a 29-fold ratio between the level of COMT activity in these two tissues in the hamster. In red blood cells, the level of COMT activity is 4- and 12-fold lower in the hamster compared to mouse and rat, respectively. When the kinetic characteristics of this enzyme were assessed in the hamster and rat kidney and liver, except for 2-hydroxymoxestrol which had an apparentKmvalue of 15–48 μM, the other catechol estrogen substrates exhibitedKmvalues ranging from 1–10 μM. Generally, theVmaxvalues were markedly higher in the rat kidney and liver than those observed in corresponding hamster tissues. The significantly lower COMT activity in the hamster liver and red blood cells suggests that under chronic estrogen treatment at high doses, the concentration of catechol estrogens in these tissues may exceed the capacity of COMT to effectively catalyse theirO-methylation into inactive metabolites. The resulting accumulation of catechol estrogens may contribute to the estrogen carcinogenicity observed in the hamster liver and kidney. Additionally, when 2-hydroxy-estrone was used as a substrate, the estrogen-induced renal carcinoma exhibited only 8.6% of the COMT activity found in the normal kidney.