IN VIVO MUTAGENICITY/CARCINOGENICITY OF HETEROCYCLIC AMINES IN TRANSGENIC MICE

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The in vivo mutagenicity and hepatocarcinogenicity of the cooked-meat derived heterocyclic amine 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx)was examined in MutaMice, transgenic mice carrying the lacZ mutational reporter gene. To evaluate the effect of c-myc overexpression on MeIQx-induced mutagenicity and carcinogenicity, MutaMice were further crossed with c-myc transgenic mice (albumin promoter/enhancer). Mice were fed MeIQx in the diet (0.06%) for 30 and 40 weeks. DNA adduct formation was measured by 32P-postlabeling and mutagenesis was examined in the lacZ gene. MeIQx-DNA adduct levels were higher in c-myc transgenic mice than in mice not carrying this transgene. C-myc overexpression increased the frequency of MeIQx-induced hepatic tumors and increased the mutant frequency in the lacZ gene. The results support the notion that overexpression of the c-myc oncogene promotes MeIQx- hepatocarcinogenesis, in part, via a mutagenic mechanism.