Tumorigenesis of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), but not enhancing effects of concomitant high-fat diet, on lung carcinogenesis in female A/J mice

Abstract

It has been reported that 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) induces liver tumors and to a lesser extent lung lesions, lymphomas and leukemias in CDF1 mice. Since a number of case control studies have pointed to a positive association between fat consumption and lung cancer, we examined the lung carcinogenic potential of MeIQx treatment concomitant with a high-fat diet using female A/J mice. Groups 1 and 2 were fed a diet supplemented with MeIQx at a concentration of 600 ppm. Groups 1 and 3 received a diet containing 20% corn oil and group 4 was fed the basal diet alone. After 1 week, 10 mice in each group were sacrificed for measurement of cytochrome P450 (CYCYP)1A2 mRNRNA in the liver and lung. The remaining mice were maintained on their respective diets until termination, 32 weeks after the initial MeIQx treatment, when lung proliferative lesions were analyzed. The incidences and multiplicities of hyperplasias and adenomas in MeIQx-treated groups (groups 1 and 2) were significantly higher than in the groups without MeIQx treatment, with a significant increase in the incidences and multiplicities of adenomas + carcinomas, as well as hyperplasia + adenomas + carcinomas (lung proliferative lesions). Lung carcinomas were observed in 1 mouse in each of the MeIQx-treated groups.