FORMATION AND REMOVAL OF DNA-ADDUCTS IN THE LIVER OF RATS CHRONICALLYFED THE FOOD-BORNE CARCINOGEN, 2-AMINO-3,8-DIMETHYLIMIDAZO[4,5-F]QUINOXALINE

Effects of chronic administration of 2-amino-3,8-dimethylimidazo[4,5-f ]quinoxaline (MeIQx) at 0.4, 8 and 400 ppm in the diet on DNA adduct f ormation and removal in the rat liver were examined by the P-32-postla beling method. The 0.4 and 8 ppm doses for 40 weeks resulted in time-d ependent increases in MeIQx-DNA adduct levels until 16 and 8 weeks, re spectively, with constant values being maintained thereafter. In the c ase of a carcinogenic dose (400 ppm) of MeIQx, the adduct levels reach ed a maximum at week 12, and then gradually decreased. Alteration of m etabolism of MeIQx during liver carcinogenesis might be related to thi s decrease in DNA adduct levels. When MeIQx administration was stopped at week 20, 60-90% of the MeIQx-DNA adducts formed with the three dos es (0.4, 8 and 400 ppm) of MeIQx were removed in a biphasic manner aft er return to a basal diet, with initial rapid removal followed by a sl ow change. No difference in the pattern of MeIQx-DNA adducts was detec ted on thin layer chromatography at any dose at any time point. Thus, it is suggested that there may be at least two types of damaged DNA, s usceptible and resistant to removal of MeIQx-DNA adducts, after chroni c administration of MeIQx.