No direct correlation between mutant frequencies and cancer incidence induced by MeIQ in various organs of Big Blue® mice

The carcinogenicity of 2-amino-3,4-dimethylimidazo[4,5-f]quinol (MeIQ) was examined in Big Blue(R) female mice with the genetic background of C57BL/6N. With the administration of 300 ppm of MeIQ in their diet for 92 weeks, the Big Blue(R) female mice developed intestinal tumors and hepatocellular carcinomas. The incidences of adenocarcinomas were 42% (8/19) in the colon and 68% (13/19) in the cecum. The incidence of hepatocellular carcinomas was 84% (16/19). No carcinomas of the intestine or the liver were induced in the control group. As we previously reported, administration of 300 ppm of MeIQ in a diet for 12 weeks induced lad mutants at the highest frequency in colonocytes, and at only less than one-tenth of the colon in cells of the liver, forestomach and bone marrow, indicating no direct correlation between the lad mutant frequency (MF) and cancer incidence (CI). The fate of cells with lad mutation in each organ should be taken into consideration to validate MF as an indicator of carcinogenic potency of a chemical in different organs. (C) 1998 Elsevier Science B.V. All rights reserved.