The food-mutagens 2-amino-1-methyl-6-phenylimidazo-[4,5-b]-pyridine (PhIP) and 2-amino-3,8-dimethylimidazo[4,5-f]-quinoxaline (MeIQx) initiate enzyme-altered hepatic foci in the resistant hepatocyte model

Abstract

The initiating activity of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and a mutagenic meat extract obtained from cooked meat was examined, using the resistant hepatocyte model (RH-model). Male Wistar rats were given a single i.p. injection of PhIP (50 or 75 mg/kg body weight) or MeIQx (50 mg/kg body weight) after a 2/3 partial hepatectomy (PH). The meat extract (corresponding to 1050 g meat/animal) was given by gastric feeding at three time points after PH. Two weeks after initiation the rats received a diet containing 0.02% 2-acetylaminofluorene for a period of 2 weeks. In the middle of this period a single dose of carbon tetrachloride was given. Rats were killed 6 weeks after the experimental start. The number of enzyme-altered (gamma-glutamyl-transferase positive) hepatic foci was significantly increased in the animals given MeIQx (P less than 0.05) and the highest dose of PhIP (P less than 0.01) whereas no effect of the meat extract was observed. The mutagenic meat extract was also studied with regard to promotive capacity in vivo, the meat extract was given in the diet of diethylnitrosamine initiated rats for a period of 6 weeks. No significant changes were detected after administration of the meat extract in the diet. It is concluded that both MeIQx and PhIP are weak initiators in the RH-model, in the same order of magnitude as the previously investigated, structurally related pyrolysis products. The meat extract was not active in the RH-model under the conditions used in this study.