卤代乙腈以硫氰酸盐形式排泄及对二甲基亚硝胺脱甲基酶的抑制作用：一种推测的代谢途径。

Haloacetonitrile excretion as thiocyanate and inhibition of dimethylnitrosamine demethylase: a proposed metabolic scheme.

作者信息

Pereira M A, Lin L H, Mattox J K

出版信息

J Toxicol Environ Health. 1984;13(4-6):633-41. doi: 10.1080/15287398409530527.

Abstract

Haloacetonitriles, contaminants present in chlorinated drinking water, were administered orally to rats, and the urinary excretion of thiocyanate was measured as an index of cyanide release. The urinary excretion of thiocyanate accounted for 14.2% of the dose of monochloroacetonitrile; 7.7-12.8% of the dose of bromochloro-, dichloro-, and dibromoacetonitrile; and 2.25% of the dose of trichloroacetonitrile. The haloacetonitriles inhibited rat-liver microsomal dimethylnitrosamine (DMN) demethylase in an in vitro assay system. Dibromo- and bromochloroacetonitrile were the most potent inhibitors of DMN demethylase, with Ki = 3-4 X 10(-5) M; dichloro- and trichloroacetonitrile were the next most potent, with Ki = 2 X 10(-4) M; and monochloroacetonitrile was the least potent inhibitor, with Ki = 9 X 10(-2) M. Trichloroacetonitrile, but not dibromoacetonitrile, when administered orally inhibited hepatic DMN demethylase activity. The relative capacity of the haloacetonitriles to inhibit DMN demethylase and to be excreted as thiocyanate did not correlate.

摘要

将存在于氯化饮用水中的污染物卤代乙腈经口给予大鼠，并测定硫氰酸盐的尿排泄量作为氰化物释放的指标。硫氰酸盐的尿排泄量占一氯乙腈剂量的14.2%；占溴氯乙腈、二氯乙腈和二溴乙腈剂量的7.7 - 12.8%；占三氯乙腈剂量的2.25%。在体外测定系统中，卤代乙腈抑制大鼠肝脏微粒体二甲基亚硝胺（DMN）脱甲基酶。二溴乙腈和溴氯乙腈是DMN脱甲基酶最有效的抑制剂，Ki = 3 - 4×10⁻⁵ M；二氯乙腈和三氯乙腈次之，Ki = 2×10⁻⁴ M；一氯乙腈是最无效的抑制剂，Ki = 9×10⁻² M。经口给予三氯乙腈可抑制肝脏DMN脱甲基酶活性，但二溴乙腈则无此作用。卤代乙腈抑制DMN脱甲基酶的相对能力与其作为硫氰酸盐排泄的相对能力不相关。