ADDUCTION OF THE HETEROCYCLIC AMINE FOOD MUTAGENS IQ AND PHIP TO MITOCHONDRIAL AND NUCLEAR-DNA IN THE LIVER OF FISCHER-344 RATS

The heterocyclic amines 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) a nd 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are carcinog ens that form DNA adducts. In the present study, we used the P-32-post labeling method to measure the levels of IQ and PhIP adducts in hepati c nuclear and mitochondrial DNA of Fischer-344 rats given a single dos e (100 mg/kg, p.o.) or 10 doses of either carcinogen. After a single d ose of IQ, adduct levels were > 2-fold higher in hepatic nuclear than in mitochondrial DNA; however, after repeated IQ exposure, the levels of adducts in nuclear and mitochondrial DNA were not significantly dif ferent. In contrast, after a single dose of PhIP, there were no signif icant differences in adduct levels in nuclear and mitochondrial DNA; h owever, after multiple doses of PhIP, adduct levels were significantly higher in mitochondrial DNA than in nuclear DNA. The percentages of i ndividual IQ or PhIP adducts were different between nuclear DNA and mi tochondrial DNA, particularly after 10 doses. With IQ, the C8-guanine adduct accounted for 72% of the total IQ adduct levels in nuclear DNA but only 40% of total adduct levels in mitochondrial DNA. After 10 dos es of PhIP, the C8-guanine adduct accounted for 48% and 15% of total a dduct levels in nuclear DNA and mitochondrial DNA respectively. In add ition, the percentage of an uncharacterized PhIP adduct was 14% in nuc lear DNA but <1% in mitochondrial DNA. The percentages of individual a dducts were approximately the same 3, 24, 120 and 240 h after a single dose of either compound, though total IQ and PhIP adduct levels appea red to decline over time in both organelles. The significance of IQ an d PhIP mitochondrial DNA adduction and the influence of distinct heter ocyclic amine adducts on carcinogenesis merit further investigation.