Expression of biotransformation enzymes in human fetal olfactory mucosa: Potential roles in developmental toxicity
Expression of biotransformation enzymes in human fetal olfactory mucosa: Potential roles in developmental toxicity
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DOI：
10.1006/taap.2000.8923
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发表时间：
2000-06-01
影响因子：
3.8
通讯作者：
Ding, XX
中科院分区：
文献类型：
--
作者：
Gu, J;Su, T;Ding, XX
高水平的细胞色素 P450 存在于哺乳动物的嗅粘膜 (OM) 中，并导致多种化合物已知的组织选择性毒性。与成人相比，围产期的嗅觉毒性可能对行为、生长和发育产生更大的影响。为了建立确定 OM 发育毒性风险的分子基础，在从妊娠第 91-125 天的人胎儿组织制备的肝和鼻微粒体中检查了几种细胞色素 P450 酶以及 NADPH-细胞色素 P450 还原酶和微粒体环氧化物水解酶的表达。通过免疫印迹测定这些生物转化酶的相对微粒体浓度。在 OM 和肝脏中均检测到 CYP2A、CYP2J2、还原酶和环氧化物水解酶的表达。这些酶在 OM 中的微粒体水平通常低于同一胎儿肝脏中的水平，但 CYP2A 相关蛋白除外，该蛋白在 OM 中的表达水平要高得多。使用RNA-PCR检测CYP2A6、CYP2A13、CYP2B6和CYP2J2 mRNA的OM表达。这些结果首次记录了人 OM 中异生生物活性细胞色素 P450 酶的产前表达，并表明人胎儿 OM 可能是 CYP2A 酶激活的母源化合物毒性的首选靶组织。 (C) 2000 年学术出版社。
High levels of cytochrome P450 are present in the olfactory mucosa (OM) in mammalian animals and contribute to the known tissue-selective toxicity of numerous chemical compounds. Olfactory toxicity in the perinatal period may have a greater impact on behavior, growth, and development than in adults. To establish a molecular basis for determining the risk of developmental toxicity in OM, the expression of several cytochrome P450 enzymes, as well as NADPH-cytochrome P450 reductase and microsomal epoxide hydrolase, was examined in hepatic and nasal microsomes prepared from human fetal tissues at gestational day 91-125. The relative microsomal concentrations of these biotransformation enzymes were determined on immunoblots. Expression of CYP2A, CYP2J2, the reductase, and epoxide hydrolase was detected in both OM and liver. The microsomal levels of these enzymes were generally lower in OM than in liver of the same fetuses, except for the CYP2A-related proteins, which were expressed in OM at much higher levels. OM expression of CYP2A6, CYP2A13, CYP2B6, and CYP2J2 mRNAs was detected using RNA-PCR. These results document, for the first time, prenatal expression of xenobiotic-bioactivating cytochrome P450 enzymes in human OM and suggest that the human fetal OM may be a preferred target tissue for the toxicity of maternally derived chemical compounds that are activated by the CYP2A enzymes. (C) 2000 Academic Press.