DNA adduct formation by 2-amino-3-methylimidazo [4,5-f] quinoline (IQ) in rat colon.

Abstract

A food-born carcinogen, 2-amino-3-methylimidazo [4,5-f] quinoline (IQ) induces cancer in the rat colon. The mechanism for colonic DNA adduct formation leading to cancer by IQ was studied using a colostomized F344 rat model. In this model, the transverse colon of the rat was colostomized, which produced a fecal stream-positive proximal colon and a negative distal colon were produced. When IQ (50 mg/kg) was administered into the distal colon of the colostomized rats (n = 5), the ratio of the DNA adduct level of the distal colonic mucosa to the paired muscular layer 24 hr after dosage was 2.02, whereas that was 1.51 and 1.37 when IQ was administered into the stomach (n = 6) and the vein (n = 5), respectively. This suggested that luminal exposure of IQ induced DNA adduct formation. Since IQ (an amine form) has no reactivity toward DNA, these findings suggested that IQ was immediately activated in the absorbed mucosal cells and reacted with DNA. However, most of the IQ absorbed was metabolically activated in the liver, distributed by blood circulation, and formed DNA adducts in the colonic mucosa and muscular layer.