Lack of modifying effects of p-phenylenediamine on induction of γ-glutamyl transpeptidase-positive foci in a medium-term bioassay system using F344 rats

Abstract

The modifying effects of p-phenylenediamine (p-PD) on liver carcinogenesis were investigated in male F344/DuCrj rats initially treated with N-nitrosodiethylamine (DEN). Two weeks after a single dose of DEN (200 mg kg , intraperitoneally), rats were given p-PD at dietary levels of 1000, 330 and 110 parts per million (ppm), or 3′-methyl-4-dimethylaminoazobenzene (3′-Me-DAB) at 600 ppm as a positive control for 6 weeks. At week 3 following DEN adminstration, all animals were subjected to partial hepatectomy. Slight retardation of body weight was observed in rats treated with p-PD at all dietary levels. Significant increases in relative liver weight were found in animals treated with 1000 ppm p-PD. Remarkable growth retardation and increased liver weight were found in rats given 3′-Me-DAB. p-PD did not significantly increase the level of γ-glutamyl transpeptidase (γ-GT) positive foci observed after DEN initiation.In contrast, 3′-Me-DAB demonstrated marked enhancing activity as evidenced by significantly increased values for γ-GT positive foci as compared with the controls given DEN alone. The results demonstrate that p-PD does not modify liver carcinogenesis in our in vivo medium-term bioassay system.