Drug metabolic enzymes in developmental toxicology
Drug metabolic enzymes in developmental toxicology
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DOI：
10.1006/faat.1996.0187
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发表时间：
1996-12-01
期刊：
影响因子：
--
通讯作者：
Raucy, JL
中科院分区：
文献类型：
--
作者：
Miller, MS;Juchau, MR;Raucy, JL
尽管我们对成年生物中环境毒物的代谢了解甚多，但关于细胞色素P450 （CYP）酶在发育过程中的作用的信息却很少。发育中的生物体是非常动态的，随着各种酶系统的激活或抑制，其代谢谱会不断变化，这可能解释了在整个发育过程中对各种毒物表现出的显著不同的敏感性。分子生物学方法的应用为这些酶在调节发育中的生物体对毒理学暴露的反应中的作用提供了重要的信息。第一个讲座将集中于CYPs在早期器官发生中的识别和作用，特别是这些酶如何影响母体和早期胚胎对有毒化学物质的反应。第二场演讲将讨论在人类发育过程中表达的CYPs的鉴定，因为成人中存在的许多酶在胎儿中不表达。第三场演讲将讨论特定代谢酶表达缺失的发育后果，重点介绍最近利用敲除小鼠来研究药物代谢酶在发育过程中的作用的研究。最后两个讲座将讨论子宫内接触有毒化学物质的短期和长期后果，以及CYP在调节发育生物体毒性反应中的作用。第一个讲座将集中讨论CYP2E1在妊娠晚期人类胎儿中的作用，以及该酶对诱导剂（如酒精）的反应。最后一个讲座将讨论CYP1A1在子宫暴露于致癌物后Ki-ras癌基因激活中的作用，作为药物遗传小鼠模型中肺部肿瘤形成的机制，(C) 1996年毒理学学会。
Although much is known about the metabolism of environmental toxicants in adult organisms, little information exists on the role of cytochrome P450 (CYP) enzymes during development, The developing organism is remarkably dynamic, presenting a constantly changing metabolic profile as various enzyme systems are activated or repressed, This may explain the markedly different sensitivities to various toxicants that are exhibited throughout the developmental period, The application of molecular biological methods has provided important information on the roles of these enzymes in modulating the response of the developing organism to toxicological exposures. The first talk will focus on the identification and role of CYPs during early organogenesis, particularly on how these enzymes influence the response of the conceptus and early embryo to toxic chemicals. The second presentation will discuss the identification of CYPs expressed during human development, as many of the enzymes present in adults are not expressed in the fetus, The third speaker will discuss the developmental consequences of loss of expression of particular metabolic enzymes, focusing on recent studies employing knockout mice to examine the role of drug metabolic enzymes during development. The last two talks will discuss some of the short- and long-term consequences of in utero exposures to toxic chemicals and the role of CYP in modulating the toxic response of the developing organism. The first of these will focus on the role of CYP2E1 in human fetuses during late gestation and the response of this enzyme to inducing agents such as alcohol, The last talk will discuss the role of CYP1A1 in the activation of the Ki-ras oncogene following in utero exposure to carcinogens as a mechanism for lung tumor formation in a pharmacogenetic mouse model, (C) 1996 Society of Toxicology.