Bioactivation in chemical teratogenesis.
Bioactivation in chemical teratogenesis.
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DOI：
10.1146/annurev.pa.29.040189.001121
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发表时间：
1989
影响因子：
12.5
通讯作者：
M. Juchau
中科院分区：
文献类型：
--
作者：
M. Juchau
在过去的十年中，人们对阐明药物和其他化学物质可以改变发育中胎儿的正常发育模式的机制的兴趣显着增加。这在很大程度上归因于最近成功地长期培养整个胚胎以及各种胚胎组织（例如肢芽）的方法。这些准备工作使得能够更直接地研究化学物质对受孕本身的直接影响，而无需复杂且经常混淆的母体因素的参与。外源代谢制剂可以纳入此类培养系统的证明使研究人员能够探究导致异常形态发生的直接和最终化学物质的性质。早期概念影响深刻的畸形生物激活的能力的证明为这些问题提供了额外的相关性。阐明化学物质的身份是阐明致病机制的第一步也是必要的一步。控制它们的产生和失活或消除速率可能是化学诱导的胚胎毒性的发生率/严重程度的主要决定因素。未来对这些现象的研究有望为化学致畸机制的发现做出重要贡献。
Within the past decade, interest has increased markedly in the elucidation of mechanisms whereby drugs and other chemicals can alter the normal developmental pattern of the developing conceptus. This has, in large measure, been attributable to the recent availability of methods for the successful long-term culture of whole embryos as well as various embryonic tissues (e.g. limb buds). These preparations have enabled a more straightforward investigation of the direct effects of chemicals on the conceptus per se, without the complicating and frequently confounding participation of maternal factors. The demonstration that exogenous metabolic preparations could be incorporated into such culture systems has enabled investigators to pursue questions about the nature of proximate and ultimate chemical species responsible for producing abnormal morphogenesis. Demonstrations of the capacity of the early conceptus to effect profound dysmorphogenic bioactivation provide additional relevance to such questions. Elucidation of the identity of the chemical species represents a first and necessary step in unravelling the pathogenic mechanism. Control of their rates of generation and inactivation or elimination are probable major determinants of incidence/severity of chemically induced embryotoxicity. Future investigations of these phenomena promise to yield key contributions to the discovery of mechanisms in chemical teratogenesis.