Glutathione conjugation of perchloroethylene in rats and mice in vitro: sex-, species-, and tissue-dependent differences.
Glutathione conjugation of perchloroethylene in rats and mice in vitro: sex-, species-, and tissue-dependent differences.
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大鼠和小鼠体外谷胱甘肽与全氯乙烯的结合：性别、物种和组织依赖性差异。
DOI：
10.1006/taap.1998.8402
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Parker,JC
中科院分区：
文献类型：
--
作者：
Lash,LH;Qian,W;Putt,DA;Desai,K;Elfarra,AA;Sicuri,AR;Parker,JC
四氯乙烯（Per）诱导的肾毒性和肾致癌性与谷胱甘肽（GSH）结合途径代谢形成S-（1，2，2-三氯乙烯基）谷胱甘肽（TCVG）有关。在Per和GSH与雄性和雌性Fischer 344大鼠的分离肾皮质细胞和肝细胞以及与雄性和雌性Fischer 344大鼠和B6 C3 F1小鼠的肾和肝细胞质和微粒体孵育中测定TCVG的形成。目的是评估代谢在对Per诱导毒性敏感性的性别和种属依赖性中的作用。一个关键的发现是Per的GSH结合发生在肾脏和肝脏中。虽然雄性和雌性大鼠离体肾细胞和肝细胞中TCVG形成量基本相似，但亚细胞组分中TCVG形成表现出明显的性别、种属和组织依赖性。这可能是由于完整细胞中存在多种代谢途径，而在本试验条件下，亚细胞组分中仅GSH结合途径具有活性。雄性大鼠和小鼠肾脏和肝脏亚细胞组分中的TCVG形成均高于雌性大鼠和小鼠的相应值。大鼠肝脏亚细胞组分中TCVG形成量约为大鼠肾脏相应组分的10倍。尽管大鼠比小鼠更容易发生Per诱导的肾肿瘤，但与大鼠相应组分相比，小鼠肾脏亚细胞组分中TCVG形成量高7- 10倍，两种性别小鼠肝脏亚细胞组分中TCVG形成量高2- 5倍。因此，尽管雄性大鼠肝脏和肾脏中TCVG形成量较高对应于其对Per诱导的肾脏肿瘤的易感性高于雌性大鼠，但小鼠中TCVG形成量明显高于大鼠，表明小鼠中Per处理过程中的其他酶促或转运步骤导致其对Per诱导的肾脏肿瘤的易感性相对较低。
Perchloroethylene (Per)-induced nephrotoxicity and nephrocarcinogenicity have been associated with metabolism by the glutathione (GSH) conjugation pathway to formS-(1,2,2-trichlorovinyl)glutathione (TCVG). Formation of TCVG was determined in incubations of Per and GSH with isolated renal cortical cells and hepatocytes from male and female Fischer 344 rats and with renal and hepatic cytosol and microsomes from male and female Fischer 344 rats and B6C3F1 mice. The goal was to assess the role of metabolism in the sex and species dependence of susceptibility to Per-induced toxicity. A key finding was that GSH conjugation of Per occurs in kidney as well as in liver. Although amounts of TCVG formation in isolated kidney cells and hepatocytes from male and female rats were generally similar, TCVG formation in subcellular fractions showed marked sex, species, and tissue dependence. This may be due to the presence of multiple pathways for metabolism in intact cells, whereas only the GSH conjugation pathway is active in the subcellular fractions under the present assay conditions. TCVG formation in kidney and liver subcellular fractions from both male rats and mice were invariably higher than corresponding values in female rats and mice. Amounts of TCVG formation in rat liver subcellular fractions were approximately 10-fold higher than in corresponding fractions from rat kidney. Although rats are more susceptible to Per-induced renal tumors than mice, amounts of TCVG formation were 7- to 10-fold higher in mouse kidney subcellular fractions and 2- to 5-fold higher in mouse liver subcellular fractions of both sexes compared to corresponding fractions from the rat. Hence, although the higher amounts of TCVG formation in liver and kidney from male rats correspond to their higher susceptibility to Per-induced renal tumors compared with female rats, the markedly higher amounts of TCVG formation in mice compared with rats suggest that other enzymatic or transport steps in the handling of Per in mice contribute to their relatively low susceptibility to Per-induced renal tumors.
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影响因子：
3.8
作者：
C. Dallas;Xiao Mei Chen;K. O'Barr;S. Muralidhara;P. Várkonyi;J. Bruckner
通讯作者：
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DOI：
--
发表时间：
1992
期刊：
Drug metabolism and disposition: the biological fate of chemicals
影响因子：
--
作者：
Sharer,JE;Duescher,RJ;Elfarra,AA
通讯作者：
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影响因子：
3.9
作者：
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影响因子：
3.9
作者：
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通讯作者：
W. Dekant
影响因子：
5.8
作者：
JONES, DP;SUNDBY, GB;ORRENIUS, S
通讯作者：
ORRENIUS, S