FORMATION AND DIFFERENTIAL REMOVAL OF C-8 AND N-2-GUANINE ADDUCTS OF THE FOOD CARCINOGEN 2-AMINO-3-METHYLIMIDAZO [4,5-F]QUINOLINE IN THE LIVER, KIDNEY, AND COLORECTUM OF THE RAT

Chronic feeding of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in the diet results in tumor formation of the liver and colorectum, but does not induce tumorigenesis in the kidney of male Fischer-344 rats. The formation and rate of removal of DNA adducts were investigated in rats given an oral dose of IQ (20 mg/kg) to determine if adduct persistenc e affects the tissue susceptibility to IQ-induced tumorigenesis. Analy sis of DNA adducts by P-32-postlabeling showed the formation of two 2' -deoxyguanosine (dG) adducts, osin-8-yl)-2-amino-3-methylimidazo[4,5-f ]quinoline (dG-C8-IQ) and anosin-N-2-yl)-amino-3-methylidazo[4,5-f]qui noline (dG-N-2-IQ). The pattern and distribution of these dG adducts w ere similar in all tissues; dG-C8-IQ and dG-N-2-IQ accounted for appro ximately 70% and 15-20%, respectively, of the observed radioactivity. Maximal DNA binding was observed in liver (7.64 +/- 1.08 adducts per 1 0(7) bases) and in colorectum (1.08 +/- 0.22 adducts per 10(7) bases) 24 h following IQ treatment, while optimal binding appeared in kidney (2.41 +/- 0.47 adducts per 10(7) bases) 72 h after treatment. Greater than 50% of the dG-C8-IQ adduct was removed from DNA of liver and kidn ey within 1 week of treatment, In contrast, the dG-N-2-IQ adduct persi sted and was the principal lesion remaining in liver and kidney 4 week s after treatment with IQ, There was no evidence for selective removal of either adduct in the colorectum over a 3 week period, and adduct r emoval appeared to be attributed to cell turnover and not due to excis ion repair processes. Therefore, the relative persistence of dG-C8-IQ and dG-N-2-IQ adducts does not appear to explain tissue susceptibility to IQ-induced neoplasia. The slow disappearance of IQ-DNA adducts sug gests that adducts may accumulate during chronic exposure to IQ. Furth er investigations on DNA adduct formation and removal in animals chron ically exposed to this carcinogen may help to explain the susceptibili ty of various organs to IQ-induced tumorigenesis.