Rao M S, Usuda N, Subbarao V, Reddy J K
Carcinogenesis. 1987 Sep;8(9):1347-50. doi: 10.1093/carcin/8.9.1347.
Male F-344 rats were fed a diet containing 2% di-(2-ethylhexyl)phthalate (DEHP) for 95 weeks. Liver nodules and/or hepatocellular carcinomas (HCC) developed in 6/10 rats fed DEHP and none were found in controls (P less than 0.005 by chi 2 test). All the nodules and HCC were negative for gamma-glutamyl transpeptidase. In the non-tumorous portions of liver, the hepatocytes contained an increased number of peroxisomes and extensive accumulation of lipofuscin. By immunocytochemical analysis, the liver peroxisomes in rats treated chronically with DEHP had visually detectable decrease in the H2O2-degrading catalase and increase in H2O2-producing fatty acyl-CoA oxidase. These results show that higher dietary level of DEHP, which causes substantially greater degree of peroxisome proliferation than the 1.2% dietary level used in the National Toxicology Program bioassay (1982, Publication no. NTP-80-37, Tech. Report Series No. 217), can induce liver tumors in male rats.
将雄性F-344大鼠喂食含2%邻苯二甲酸二(2-乙基己基)酯(DEHP)的饲料95周。在喂食DEHP的10只大鼠中,有6只出现肝结节和/或肝细胞癌(HCC),而对照组未发现此类情况(经卡方检验,P<0.005)。所有结节和HCC的γ-谷氨酰转肽酶均为阴性。在肝脏的非肿瘤部分,肝细胞中过氧化物酶体数量增加,脂褐素大量积累。通过免疫细胞化学分析,长期用DEHP处理的大鼠肝脏过氧化物酶体中,可目视检测到降解过氧化氢的过氧化氢酶减少,而产生过氧化氢的脂肪酰辅酶A氧化酶增加。这些结果表明,与国家毒理学计划生物测定(1982年,出版物编号NTP-80-37,技术报告系列第217号)中使用的1.2%饮食水平相比,更高饮食水平的DEHP可导致过氧化物酶体增殖程度大幅增加,从而可诱导雄性大鼠发生肝肿瘤。