Lack of modification of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) rat hepatocarcinogenesis by caffeine, a CYP1A2 inducer, points to complex counteracting influences

Abstract

2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), one of the most abundant carcinogenic heterocyclic amines in cooked foods, is speculated to be a human liver carcinogen. To test the hypothesis that it is metabolically activated by CYP1A2, we here investigated the effects of caffeine as a CYP1A2 inducer on MeIQx induced rat hepatocarcinogenesis in a medium-term liver bioassay system. Unexpectedly, no modifying effects of caffeine on MeIQx-induced hepatocarcinogenesis were evident, although up-regulation of CYP1A2 and NAT2 were detected. Therefore, mRNAs extracted from GST-P positive foci and the surrounding liver tissue in each group were analyzed to explore mechanisms in detail. The results suggest that suppression of syndecan-2 (Sdc2) and induction of cell cycle arrest through a p21-dependent pathway might have counter-acted any promotion effects of up-regulation of CYP1A2.