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 from 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 liver, 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 adducts are related to those in internal organs. Male Fischer-344 rats received IQ as an oral dose (5 or 50 mg/kg, starting on day 0) by daily gavage (1, 8 or 15 days of treatment). Using 32P-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 those in the organs and adduct formation was highest in the liver, followed by the lungs, kidneys, stomach, large intestine, WBC and small intestine. Accumulation of adducts occurred in all organs and in WBCs in a dose- and time-dependent manner. For all organs, IQ-DNA adduct formation was strongly correlated with those in WBCs. It is concluded that IQ-DNA adducts in WBCs are qualitatively and quantitatively directly related to those in internal organs, independent of the target organ specificity of the carcinogenic effect of IQ.
Schut
H A
HA
Department of Pathology, Medical College of Ohio, Toledo 43699.
Herzog
C R
CR
Cummings
D A
DA
D000284:Administration, Oral; D000818:Animals; D002273:Carcinogens / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D009153:Mutagens / Q000378:metabolism*; D011804:Quinolines / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344
D002273:Carcinogens; D009153:Mutagens; D011804:Quinolines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; D004247:DNA