Carcinogenic risk assessment of MeIQx and PhIP in a newborn mouse two-stage tumorigenesis assay.

A newborn mouse two-stage tumorigenesis assay was evaluated as a possible alternative to chronic rodent carcinogenicity bioassays by investigating the carcinogenicity of two major heterocyclic amines, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). One week after birth, Crj:CD-1 mice of both sexes were subcutaneously administered N-nitrosobis(2-oxopropyl)amine (BOP) at a dose of 50 mg/kg as an initiation treatment and starting 2 weeks thereafter they were fed diets supplemented with MeIQx at concentrations of 300, 30, 3 or 0 ppm or PhIP at 200, 50, 10 or 0 ppm for 23 weeks. Animals in all groups predominantly developed tumors of the lung and liver. Pulmonary adenomas and adenocarcinomas were observed in all groups with high incidences, without any significant differences between the groups. MeIQx and PhIP did not influence the multiplicity except in the group given 10 ppm PhIP where it significantly increased the number of pulmonary adenomas (P < 0.05). Similarly, hepatocellular adenomas and carcinomas were found in all groups with high incidences, and again MeIQx and PhIP did not increase their incidences or multiplicities. Although adenomas and carcinomas in the nasal cavity, and acinar cell foci in the pancreas were infrequently found, none of these incidences were increased with the MeIQx or PhIP treatments. These results thus suggest that the tumor-promoting effects of MeIQx or PhIP may be rather weak, if present, as far as this newborn two-stage model is concerned, and the possibility that the dose of BOP was too high to detect the tumor-promoting effects of MeIQx or PhIP by masking them cannot be completely ruled out.