Agency for Toxic Substances and Disease Registry, US Department of Health and Human Services, Atlanta, GA 30333, USA.
Regul Toxicol Pharmacol. 2011 Apr;59(3):364-74. doi: 10.1016/j.yrtph.2011.01.013. Epub 2011 Feb 2.
Humans are simultaneously exposed to multiple chemicals in the environment. Many of the chemicals use the same enzymes in their metabolic pathways. Competitive inhibition may occur as one of the possible interactions between the xenobiotics in human body. For example, many volatile organic compounds (VOCs) are metabolized using P450 enzymes, specifically CYP2E1. Inheritable gene alterations may result in changes of function of the enzymes in different human subpopulations. Variations in quantity and/or quality of particular isoenzymes may cause differences in the metabolism of VOCs. These variations may cause higher sensitivity in certain populations. Using examples of three different mixtures, this review paper outlines the variances in CYP2E1 isoenzymes, effect of exposure to such mixtures on sensitive populations, and approaches to mixtures risk assessment.
人类同时暴露于环境中的多种化学物质中。许多化学物质在其代谢途径中使用相同的酶。作为人体中外源化学物质之间可能存在的相互作用之一，可能会发生竞争性抑制。例如，许多挥发性有机化合物（VOCs）使用 P450 酶，特别是 CYP2E1 进行代谢。遗传基因改变可能导致不同人群中酶的功能发生变化。特定同工酶的数量和/或质量的变化可能导致 VOCs 代谢的差异。这些变化可能导致某些人群的敏感性更高。本文通过三个不同混合物的例子，概述了 CYP2E1 同工酶的差异、此类混合物对敏感人群的影响，以及混合物风险评估的方法。
