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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC005789-04
Application #
6100877
Study Section
Special Emphasis Panel (LEC)
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code