Nature of the enhancement of hepatic uridine diphosphate glucuronyltransferase activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats (original) (raw)

~-After single low-level oral doses of).3.7.X-tetrachlorodiben/o-/1-dio~in (TCDD) to rats. hcpatic microsomal p-nitrophenol (PNP) glucuronqltransferasc acti\itj was elckated approximately h-fold. whereas the hepatic glucuronyltransfcrase conjugating testosterone or estrone was unaflectcd. Solubilized and purified PNP glucuronyltransferasc and steroid glucuronyltransferases from control and TCDDtreated rats exhibited the same rclativc activities (TC'DD:control) as when the cn~ymcs were bound to the cndoplasmic reticulum. Elevation of PNP glucuronqltransfer~~sc was still evident 73 days after a single oral dose of 25 lg TCDD;kg. Fcmalc rats WI-C more susceptible to TCDD actions on liwr microsomal PNP glucuronyltransfcrasc than males. The cffccts of TCDD trcatmcnt on PNP glucuron~ltransfcrase appcarcd to be related to increased amounts of liver enzyme for the following reasons: (1) K,, values for PNP and UDPGA were unchanged by TCDD treatments; (2) the magnitude of the TCDD-induced increase of PNP glucuronyltransfcrase activity was the same whcthcr enrqme actiwty MBS measured in the prcscnce or absence of Mg" or Triton X-100; (3) TCDD, v,hen added irk rirw, had no detectable effect on enzyme activity: (4) TCDD treatment of rats did not change total hepatic microsomal phospholipid or cholesterol contents; (5) pH optima were unatrectcd by TCDD trcatmcnt; (6) soluhiliratlon of ewyme was not accompanied by a change in the TCDD Induction cffcct; and (7) actinomycin D appeared to block the imtial phase of induction 2.3.7,8-Tetrachlorodibenzo-p-dioxin (TCDD). a possible contaminant of 2,3,7,8-Tetrochlorodibenzo-p-dioxin