Cashman J R, Olsen L D, Young G, Bern H
Department of Pharmaceutical Chemistry and Liver Center, School of Pharmacy, University of California, San Francisco 94143-0446.
Chem Res Toxicol. 1989 Nov-Dec;2(6):392-9. doi: 10.1021/tx00012a007.
The in vitro liver microsomal oxidation of eptam (ethyl N,N-dipropylthiocarbamate) in the presence of freshwater and salt water adapted striped bass liver microsomes was investigated. In freshwater hepatic microsomes from striped bass, eptam is S-oxygenated in a process consistent with the involvement of monooxygenase activity. In contrast, both eptam S-oxide and eptam sulfone are formed in microsomes from salt water adapted striped bass microsomes in a process that is independent of monooxygenase activity and consistent with a role of cooxidation by hydroperoxy fatty acids. The mechanism of oxidation of eptam by hydroperoxy fatty acids may involve radical species. Both eptam S-oxide and eptam sulfone are efficient carbamylating agents toward thiol nucleophiles and react with substituted thiophenols to produce thiocarbamates while eptam itself is relatively stable to trans thiocarbamylation. Monooxygenase-catalyzed S-oxygenation of eptam in freshwater striped bass hepatic microsomes may represent a bioactivation route, which may explain the toxicity of thiocarbamate herbicides such as eptam toward freshwater fish.
研究了在淡水和咸水适应的条纹鲈鱼肝微粒体存在下，eptam（N,N-二丙基硫代氨基甲酸乙酯）的体外肝微粒体氧化情况。在条纹鲈的淡水肝微粒体中，eptam通过与单加氧酶活性相关的过程进行S-氧化。相比之下，eptam S-氧化物和eptam砜在咸水适应的条纹鲈微粒体中形成，该过程独立于单加氧酶活性，并且与氢过氧脂肪酸的共氧化作用一致。氢过氧脂肪酸对eptam的氧化机制可能涉及自由基。eptam S-氧化物和eptam砜都是针对硫醇亲核试剂的有效氨甲酰化剂，并且与取代的硫酚反应生成硫代氨基甲酸盐，而eptam本身对反式硫代氨基甲酰化相对稳定。淡水条纹鲈肝微粒体中eptam的单加氧酶催化的S-氧化可能代表一种生物活化途径，这可能解释了硫代氨基甲酸盐除草剂如eptam对淡水鱼的毒性。
