Fedtke N, Certa H, Ebert R, Wiegand H J
Hüls Aktiengesellschaft, UB W/U-Ps Biologie-Toxikologie, Marl, Germany.
Arch Toxicol. 1994;68(4):217-23. doi: 10.1007/s002040050060.
Groups of male and female F-344 rats and B6C3F1 mice were exposed to 15,000 ppm ethyl chloride (monochloroethane, ECL) or to air for 5 days (6 h/day). In this report, features of GSH-dependent ECL metabolism in the animals are described. A concurrent report describes the features of the cytochrome P450-dependent oxidative ECL metabolism (Fedtke et al. 1994). ECL conjugation to GSH in hepatic cytosolic fractions was catalyzed by GSH S-transferases. The specific activities were 0.16 +/- 0.03 and 0.17 +/- 0.01 nmol ECL conjugated/(min mg protein) in air treated male and female F-344 rats, respectively. These activities were not significantly altered by the ECL treatment. Compared with rats, the GSH-transferase activities towards ECL were generally higher in male and female B6C3F1 mice (0.71 +/- 0.19 and 1.01 +/- 0.19, respectively) and were slightly decreased by ECL treatment. The ECL conjugation to GSH resulted in a marked reduction of the GSH concentration in the lung and the uterus after 5 days of exposure. In contrast, liver and kidney GSH concentrations were affected only to a minor degree. Formed S-ethyl-glutathione was converted to the mercapturic acid S-ethyl-N-acetyl-L-cysteine (SENACys), which was detected in the urine of both species. In addition, the non-acetylated intermediate S-ethyl-L-cysteine (SECys) was excreted in mouse urine but not in rat urine. The cumulative amounts of SENACys and SECys excreted after 5 days were up to fivefold higher in mice than in rats and the excretion kinetics were species specific.(ABSTRACT TRUNCATED AT 250 WORDS)
将雄性和雌性F-344大鼠以及B6C3F1小鼠分组，使其暴露于15,000 ppm的氯乙烷（一氯乙烷，ECL）或空气中5天（每天6小时）。在本报告中，描述了动物体内谷胱甘肽依赖性ECL代谢的特征。一篇同期报告描述了细胞色素P450依赖性氧化ECL代谢的特征（费德克等人，1994年）。谷胱甘肽S-转移酶催化肝胞质组分中ECL与谷胱甘肽的结合。在空气处理的雄性和雌性F-344大鼠中，比活性分别为0.16±0.03和0.17±0.01 nmol ECL结合物/（分钟·毫克蛋白质）。这些活性未因ECL处理而发生显著改变。与大鼠相比，雄性和雌性B6C3F1小鼠对ECL的谷胱甘肽转移酶活性通常更高（分别为0.71±0.19和1.01±0.19），且经ECL处理后略有降低。暴露5天后，ECL与谷胱甘肽的结合导致肺和子宫中谷胱甘肽浓度显著降低。相比之下，肝脏和肾脏中的谷胱甘肽浓度仅受到轻微影响。形成的S-乙基谷胱甘肽转化为硫醚氨酸S-乙基-N-乙酰-L-半胱氨酸（SENACys），在两个物种的尿液中均有检测到。此外，非乙酰化中间体S-乙基-L-半胱氨酸（SECys）在小鼠尿液中排出，但不在大鼠尿液中排出。5天后排出的SENACys和SECys的累积量在小鼠中比在大鼠中高出五倍，且排泄动力学具有物种特异性。（摘要截断于250字）
