Du J T, Sandoz J P, Tseng M T, Tamburro C H
J Toxicol Environ Health. 1979 Nov;5(6):1119-32. doi: 10.1080/15287397909529818.
Sprague-Dawley rats were exposed to vinyl chloride to determine the earliest sequential biochemical changes occurring with liver injury before anglosarcoma development. Activity of glucose-6-phosphatase, a key gluconeogenic enzyme in the liver microsomal fraction, decreased 25% with respect to controls after 70 h of exposure. Glucose-6-phosphate dehydrogenase activity increased twofold after more than 100 h of exposure. Nonprotein sulfhydryl levels (glutathione and/or cysteine) showed a slight but progressive elevation, whereas glutathione reductase activity increased 50-60% during exposure to vinyl chloride.NADPH-cytochrome c reductase and mixed function oxidase were unchanged in the same microsomal fraction. There markers of liver mitochondrial, cytosol, and microsomal function. No significant histological changes were found on light microscopic examination during this exposure period. However, with electron microscopy, dilation of rough endoplasmic reticulum was seen in the animals exposed for more than 137 h. These enzymatic changes are considered to reflect early hepatocellular adaptation to vinyl chloride exposure with very mild or limited hepatocellular injury in its earliest stage.
将Sprague-Dawley大鼠暴露于氯乙烯中，以确定在血管肉瘤发生之前肝脏损伤时最早出现的一系列生化变化。葡萄糖-6-磷酸酶是肝脏微粒体部分中的一种关键糖异生酶，暴露70小时后，其活性相对于对照组降低了25%。暴露100多小时后，葡萄糖-6-磷酸脱氢酶活性增加了两倍。非蛋白巯基水平（谷胱甘肽和/或半胱氨酸）呈现轻微但持续的升高，而在暴露于氯乙烯期间，谷胱甘肽还原酶活性增加了50%-60%。在同一微粒体部分中，NADPH-细胞色素c还原酶和混合功能氧化酶没有变化。这些是肝脏线粒体、胞质溶胶和微粒体功能的标志物。在此暴露期间，光镜检查未发现明显的组织学变化。然而，通过电子显微镜观察，暴露超过137小时的动物出现了粗面内质网扩张。这些酶的变化被认为反映了早期肝细胞对氯乙烯暴露的适应，在其最早阶段肝细胞损伤非常轻微或有限。
