EFFECT OF 3-METHYLCHOLANTHRENE INDUCTION ON THE DISTRIBUTION AND DNA ADDUCTION OF 2-AMINO-3-METHYLIMIDAZO[4,5-F]QUINOLINE (IQ) IN F344 RATS

3-Methylcholanthrene (3MC) is a potent inducer of the cytochrome P450I A family of enzymes that catalyses the metabolic activation of the foo d mutagen/carcinogen 2-amino-3-methylimidazo-[4,5-f]quinoline (IQ). We have examined the effect of pretreatment with 3MC on the distribution and DNA adduct formation of IQ in male Fischer F344 rats. 3 hr after a single dose of [C-14]IQ (10 mg/kg body weight, by gavage), the level of radioactivity in extrahepatic tissues was 30-70% less in 3MC-pretr eated rats than in vehicle control rats. Although the level of radioac tivity in the liver did not change after 3MC pretreatment, IQ-DNA addu ct levels, measured by the P-32-postlabelling method, were 60% lower i n the livers of 3MC-pretreated rats than those of control rats, and 83 -97% lower in extrahepatic tissues such as the kidneys, colon, small i ntestine, bladder, heart and lung. IQ-DNA adducts in the testes and br ain were found in control rats but were not detected in 3MC-pretreated rats. The rate of removal of IQ-DNA adducts from the livers of contro l and 3MC-pretreated animals was the same from 3 to 48 hr. At 48 hr, t he adduct level in 3MC-pretreated rats remained lower than that seen i n the control rats. The data suggest that 3MC induction of the P450IA family of cytochromes in vivo results in an increased rate of IQ detox ification.