Hui Q Y, Armstrong C, Laver G, Iverson F
Institute of Health, Chinese Academy of Medical Sciences, Beijing.
Toxicol Lett. 1988 Jun;41(3):231-7. doi: 10.1016/0378-4274(88)90059-8.
Ethylenethiourea (ETU), a metabolite and degradation product of the ethylenebisdithiocarbamate fungicides, is a substrate for the flavin-dependent monooxygenase (FMO), a microsomal NADPH requiring enzyme that can oxidize ETU, as well as for the cytochrome P-450 enzyme system. The present study shows that the mouse metabolises ETU preferentially via the FMO system. FMO activity decreases as male, but not female mice, increase in age to 30 weeks. This difference in activity is reflected in decreased overall metabolism of ETU and in a decreased FMO-mediated binding of radiolabelled ETU to mouse liver microsomal protein. The rapid metabolism of ETU by the FMO system may contribute to the lack of acute toxicity and teratogenicity exhibited by the mouse relative to the rat. However, the FMO-mediated binding of ETU metabolites to mouse liver protein is consistent with the chronic hepatotoxicity exhibited by ETU in this species.
乙撑硫脲（ETU）是亚乙基双二硫代氨基甲酸盐类杀菌剂的一种代谢产物和降解产物，它是黄素依赖性单加氧酶（FMO）的底物，FMO是一种需要微粒体NADPH的酶，能够氧化ETU，同时它也是细胞色素P-450酶系统的底物。本研究表明，小鼠优先通过FMO系统代谢ETU。随着雄性小鼠（而非雌性小鼠）年龄增长至30周，FMO活性降低。这种活性差异反映在ETU整体代谢的减少以及FMO介导的放射性标记ETU与小鼠肝脏微粒体蛋白结合的减少上。FMO系统对ETU的快速代谢可能是小鼠相对于大鼠缺乏急性毒性和致畸性的原因。然而，FMO介导的ETU代谢产物与小鼠肝脏蛋白的结合与ETU在该物种中表现出的慢性肝毒性一致。
