MECHANISM OF DI(2-ETHYLHEXYL)PHTHALATE HEPATOTOXICITY

在一项为期两年的毒理学/致癌性研究中 国家毒理学计划邻苯二甲酸二(2-乙基己基)酯 (DEHP)在B6C3F1小鼠中被发现是肝癌的致癌物，并且 F334只大鼠。由于DEHP也会引起过氧化物酶的增殖， 有人认为这种化学物质的致癌性 可能与H202产生过多的过氧化物体有关。 该项目的目标是检查在 过氧化物型脂肪酰辅酶A产生的过氧化氢浓度 大鼠和小鼠肝脏的氧化和过氧化氢酶活性 用DEHP治疗。进一步评估是否涉及 DEHP诱导氧还原的活性中间体 肝毒性将由(A)的测量结果确定 清除有毒氧气产物的酶的活性 (过氧化氢酶、超氧化物歧化酶、谷胱甘肽过氧化物酶)，(B) 脂质过氧化和(C)超氧阴离子自由基 制作。新的研究已经开始描述 过氧化酶体诱导的化学要求 体外培养的大鼠肝细胞的增殖。

In a two-year toxicology/carcinogenicity study conducted by the National Toxicology Program, di(2-ethylhexyl)phthalate (DEHP) was found to be hepatocarcinogenic in B6C3F1 mice and F334 rats. Since DEHP also causes peroxisome proliferation, it has been suggsted that the carcinogenicity of this chemical may be related to excessive peroxisomal production of H202. It is the objective of this project to examine the changes in H2O2 concentrations resulting from peroxisomal fatty acyl-CoA oxidation and catalase activity in livers of rats and mice treated with DEHP. Further assessment of an involvement of ractive intermediates of oxygen reduction in DEHP induced hepatotoxicity will be made from measurements of (a) activities of enzymes that eliminate toxic oxygen products (catalase, superoxide dismutase, glutathione peroxidase), (b) lipid peroxidation, and (c) superoxide anion radical production. New studies have begun to characterize the chemical requirements for induction of peroxisome proliferation in isolated rat hepatocytes.