Department of Toxicology, School of Pharmacy, College of Health Sciences, The University of Louisiana at Monroe, 700 University Avenue, Sugar Hall #306, Monroe, LA 71209, USA.
Environ Toxicol Pharmacol. 2004 Nov;18(2):143-8. doi: 10.1016/j.etap.2004.02.010.
The objective of this study was to test whether a binary mixture (BM) of chloroform (CHCl(3)) and thioacetamide (TA) causes a dose-dependent liver injury and an opposing tissue repair. Liver injury was assessed by plasma alanine aminotransferase (ALT) and histopathology. Tissue repair was measured by [(3)H-CH(3)]-thymidine ((3)H-T) incorporation into hepatonuclear DNA and PCNA over a time course of 0-72h. Male Sprague-Dawley (S-D) rats received six- and five-fold dose ranges of TA and CHCl(3), respectively. ALT levels and (3)H-T incorporation were in complete agreement with corresponding microscopic observations, and only ALT elevation and (3)H-T incorporation data are presented here. Liver injury observed after exposure to BM was no different than addition of injuries caused by individual compounds. Tissue repair was prompt and adequate, leading to recovery from injury and animal survival. Tissue repair is dose-dependent and plays central role in the hepatotoxic outcome.
本研究旨在测试三氯甲烷 (CHCl(3)) 和硫代乙酰胺 (TA) 的二元混合物 (BM) 是否会导致剂量依赖性肝损伤和相反的组织修复。通过血浆丙氨酸氨基转移酶 (ALT) 和组织病理学评估肝损伤。通过 [(3)H-CH(3)]-胸腺嘧啶核苷 ((3)H-T) 在 0-72 小时的时间过程中掺入肝核 DNA 和 PCNA 来测量组织修复。雄性 Sprague-Dawley (S-D) 大鼠分别接受 TA 和 CHCl(3) 的六倍和五倍剂量范围。ALT 水平和 (3)H-T 掺入与相应的显微镜观察完全一致,此处仅呈现 ALT 升高和 (3)H-T 掺入数据。暴露于 BM 后观察到的肝损伤与单个化合物引起的损伤没有区别。组织修复迅速且充分,导致损伤恢复和动物存活。组织修复呈剂量依赖性,在肝毒性结果中起核心作用。