ACCUMULATION OF DNA-ADDUCTS OF 2-AMINO-3-METHYLIMIDAZO[4,5-F] QUINOLINE (IQ) IN TISSUES AND WHITE BLOOD-CELLS OF THE FISCHER-344 RAT AFTER MULTIPLE ORAL DOSING

The genotoxic effect of an environmental chemical may be estimated fro m the concentration of its DNA adducts in peripheral white blood cells (WBCs). The food mutagen 2-amino-3 -methylimidazo[4,5-f]quinoline (IQ ) is carcinogenic in the Fischer-344 rat, affecting principally the li ver, small intestine and large intestine. In the present study we have determined whether DNA adducts of IQ are present in circulating WBCs of rats after single or multiple oral doses of IQ and how these adduct s are related to those in internal organs. Male Fischer-344 rats recei ved IQ as an oral dose (5 or 50 mg/kg, starting on day 0) by daily gav age (1, 8 or 15 days of treatment). Using P-32-postlabeling assays, IQ -DNA adducts were isolated and quantitated in organs and WBCs on days 1, 8 and 15. Adduct patterns in WBCs were qualitatively similar to tho se in the organs and adduct formation was highest in the liver, follow ed by the lungs, kidneys, stomach, large intestine, WBC and small inte stine. Accumulation of adducts occurred in all organs and in WBCs in a dose- and time-dependent manner. For all organs, IQ-DNA adduct format ion was strongly correlated with those in WBCs. It is concluded that I Q-DNA adducts in WBCs are qualitatively and quantitatively directly re lated to those in internal organs, independent of the target organ spe cificity of the carcinogenic effect of IQ.