Induction of aryl hydrocarbon hydroxylase activity in the rat prostate glands by 2,3,7,8-tetrachlorodibenzo-p-dioxin

IP Lee and K Suzuki

Because of the interest in male reproductive tract toxicity, we determined the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on cytochrome P-450 levels and the specific activity of aryl hydrocarbon hydroxylase (AHH), epoxide hydrase and glutathione S-transferase in the rat prostate glands after a single oral dose of TCDD (10 microgram/kg b.wt.). The maximum induction of AHH activity and cytochrome P-450 levels in the prostate glands was approximately 200- and 6.5-fold that of controls. After TCDD treatment, the peak induction of AHH activity and cytochrome P-450 levels in the prostate glands was observed at 16 and 48 hr, respectively; however, the specific activity of epoxide hydrase or glutathione S-transferase in prostate glands was not induced at any time after TCDD treatment. TCDD-induction of AHH and cytochrome P-450 contents can be completely inhibited by a single pretreatment with either actinomycin D or cycloheximide, suggesting TCDD induces de novo synthesis of specific proteins. Dramatic increases in AHH activity (200-fold increase) were associated with the new formation of cytochrome P-450 in the rat prostate glands after a single oral dose of TCDD. The biological significance of such a dramatic increase of prostatic AHH activity and the emergence of new cytochrome P-446 in rat prostate glands is unknown at the present time.

Volume 215, Issue 3, pp. 601-605, 12/01/1980
Copyright © 1980 by American Society for Pharmacology and Experimental Therapeutics