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 colo-rectum of male Fischer-344 rats given a single oral dose of IQ (20 mg/kg). The pattern and distribution of DNA adducts examined by 32P-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 approximately 50-70% of the observed radioactivity, followed by (deoxyguanosin-N2-yl)-2-amino-3-methylimidazo[4,5-f]quinoline (dG-N2-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.
Turesky
R J
RJ
Nestec Ltd., Research Centre, Vers-chez-les-Blanc, Lausanne, Switzerland.
Markovic
J
J
D000818:Animals; D002273:Carcinogens / Q000378:metabolism* / Q000633:toxicity; D003106:Colon / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D018736:DNA Adducts / Q000032:analysis / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D007668:Kidney / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010761:Phosphorus Radioisotopes; D011804:Quinolines / Q000378:metabolism* / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D012007:Rectum / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism
D002273:Carcinogens; D018736:DNA Adducts; D010761:Phosphorus Radioisotopes; D011804:Quinolines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline