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.
Snyderwine, Elizabeth G; Yoon, Hae-Seong; Knight-Jones, Laundette P et al. (2003) Mutagenesis and DNA adduct formation in the mouse mammary gland exposed to 2-hydroxyamino-1-methyl-6-phenylimidazo-[4,5-b]pyridine in whole organ culture. Mutagenesis 18:7-12 |
Ryu, D Y; Pratt, V S; Davis, C D et al. (1999) In vivo mutagenicity and hepatocarcinogenicity of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in bitransgenic c-myc/lambda lacZ mice. Cancer Res 59:2587-92 |
Thorgeirsson, S S; Ryu, D Y; Weidner, V et al. (1999) Carcinogenicity and mutagenicity of heterocyclic amines in transgenic mouse models. Cancer Lett 143:245-7 |