Infant mouse as a sensitive bioassay system for carcinogenicity of N-nitroso compounds

Five groups of 48, C57BLxC3H F1, male mice, 15 days old, were administered NDEA intraperitoneally at the following levels: 0.0 (saline only), 0.625, 1.25, 2.50 and 5.00 microgram per g body weight, in a single dose. Groups of eight mice from each of the dose levels were killed at 40, 50, 60, 70, 80 and 90 weeks of age. The nodular liver lesions were classified s (a) focal areas of non-specific cellular changes, (b) hyperplastic nodules, (c) hepatocellular adenomas and (d) hepatocellular carcinomas. Regardless of the dose, all the animals developed hepatocellular carcinomas. The average latent periods, however, were inversely proportional to dose, being 66 weeks with the lowest dose and 44 weeks with the highest dose. The multiplicity and the average weight of the early nodular lesions (50 weeks) was directly related to th NDEA dose. Thus the higher multiplicity was associated with faster emergence of hepatocellular carcinomas. The high susceptibility to hepatocellular carcinogenesis, in association with the short latency, makes the infant mouse a sensitive bioassay system for assessing the carcinogenic potential of N-nitroso compounds.