Factors affecting the induction of DT-diaphorase by 2,3,7,8-tetrachlorodibenzo-p-dioxin

The compound 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a toxic contaminant in some preparations of chlorinated phenols, is a potent inducer of a number of enzymes including rat liver DT-diaphorase (EC 1.6.99.2). The present study has shown that the induction of DT-diaphorase by TCDD is prevented by prior administration of actinomycin-D. In addition, it has been shown that administration of TCDD brings about an increase in NADPH-diaphorase activity in a number of extrahepatic tissues of the rat. In contrast to the rat, the adult male guinea pig, the species most sensitive to the toxic effects of TCDD, exhibits little or no increase in DT-diaphorase activity in various tissues in response to TCDD administration. The compound 1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin (OCDD) is much less toxic than TCDD. OCDD was also shown to be much less potent as an inducer of rat liver DT-diaphorase than TCDD.