INDUCTION OF DT-DIAPHORASE IN RIBOFLAVIN-DEFICIENT RATS BY XENOBIOTICTREATMENT

This paper describes the induction of DT-diaphorase by xenobiotic trea tment of riboflavin-deficient rats. Upon injection of beta-naphthoflav one once a day for 3 successive days into male Wistar rats fed a ribof lavin-supplemented diet for 4 weeks, the activity of DT-diaphorase in the cytosolic, mitochondrial, and microsomal fractions of rat liver in creased several fold compared with that of the vehicle control. In the case of rats fed a riboflavin-deficient diet for 4 weeks, DT-diaphora se activity in the cytosolic fraction was markedly decreased and that in microsomes was somewhat diminished, whereas the activity in mitocho ndrial fraction did not change, compared with that of the above contro l. However, when the deficient rats were injected with beta-naphthofla vone intraperitoneally, DT-diaphorase activity in the cytosolic, mitoc hondrial, and microsomal fractions increased in spite of a significant decrease in flavin levels in the body. These results indicate that DT -diaphorase is actually induced even under conditions of riboflavin de ficiency and that the apoprotein of the enzyme takes up FAD to become holoenzyme, suggesting a redistribution of FAD among various flavoprot eins in the liver of riboflavin-deficient rats upon administration of a xenobiotic. Among the activities of other flavoenzymes examined, the occurrence of the apoenzyme of glutathione reductase, thioredoxin red uctase or NADPH-cytochrome P450 reductase was found upon the injection of beta-naphthoflavone in the riboflavin-deficient rats, which might be an indication of the above-mentioned redistribution.