Rj. Turesky et J. Markovic, DNA ADDUCT FORMATION OF THE FOOD CARCINOGEN 2-AMINO-3-METHYLIMIDAZO[4,5-F]QUINOLINE (IQ) IN LIVER, KIDNEY AND COLO-RECTUM OF RATS, Carcinogenesis, 16(9), 1995, pp. 2275-2279
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 distributi
on of DNA adducts examined by P-32-postlabeling was similar in all tis
sues, osin-8-yl)-2-amino-3-methylimidazo[4,5-f]quinoline (dG-C8-IQ) wa
s the principal adduct identified and it accounted for similar to 50-7
0% of the observed radioactivity, followed by in-N-2-yl)-2-amino-3-met
hylimidazo[4,5-f]quinoline (dG-N-2-IQ) which accounted for 15-20% of t
he radioactivity. Twenty-four hours after IQ treatment, DNA modificati
on was greatest in the liver at a level of 7.64 +/- 1.08 adducts per 1
0(7) bases, followed by kidney at 2.04 +/- 0.32 adducts per 10(7) base
s, 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 chro
nic feeding studies with IQ; however, tumors are not formed in the kid
ney. Therefore, factors in addition to IQ-guanine adduct formation, su
ch as adduct persistence, error-prone repair, and tumor promotion must
contribute to organ susceptibility of IQ-induced carcinogenesis.