Absence of {gamma}-glutamyl transpeptidase activity in neoplastic lesions induced in the liver of male F-344 rats by di-(2-ethylhexyl)phthalate, a peroxisome proliferator

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 incontrols (P<0.005 by x² test). All the nodules and HCC werenegative for -glutamyl transpeptidase. In the non-tumorous portionsof liver, the hepatocytes contained an increased number of peroxisomesand extensive accumulation of lipofuscin. By immunocyto-chemicalanalysis, the liver peroxisomes in rats treated chronicallywith DEHP had visually detectable decrease in the H₂O₂-degradingcatalase and increase in H₂O₂-producing fatty acyl-CoA oxidase.These results show that higher dietary level of DEHP, whichcauses substantially greater degree of peroxisome proliferationthan the 1.2% dietary level used in the National ToxicologyProgram bioassay (1982, Publication no. NTP-80-37, Tech. ReportSeries No. 217), can induce liver tumors in male rats.