DNA ADDUCT FORMATION OF THE FOOD CARCINOGEN 2-AMINO-3-METHYLIMIDAZO[4,5-F]QUINOLINE (IQ) IN LIVER, KIDNEY AND COLO-RECTUM OF RATS

DNA adducts of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) have been measured in the liver, kidney, and colorectum of male Fischer-344 rats given a single oral dose of IQ (20 mg/kg). The pattern and distribution of DNA adducts examined by P-32-postlabeling was similar in all tissues, N-(Deoxyguanosin-8-yl)-2-amino-3-methylimidazo[4,5-f]quinoline (dG-C8-IQ) was the principal adduct identified and it accounted for similar to 50-70% of the observed radioactivity, followed by (deoxyguanosin-N-2-yl)-2-amino-3-methylimidazo[4,5-f]quinoline (dG-N-2-IQ) which accounted for 15-20% of the radioactivity. Twenty-four hours after IQ treatment, DNA modification was greatest in the liver at a level of 7.64 +/- 1.08 adducts per 10(7) bases, followed by kidney at 2.04 +/- 0.32 adducts per 10(7) bases, and colorectum at 1.08 +/- 0.22 adducts per 10(7) bases. Liver and colo-rectum are target tissues of tumorigenesis in the rat during chronic feeding studies with IQ; however, tumors are not formed in the kidney. Therefore, factors in addition to IQ-guanine adduct formation, such as adduct persistence, error-prone repair, and tumor promotion must contribute to organ susceptibility of IQ-induced carcinogenesis.