2,3,7,8-Tetrachlorodibenzo-p-dioxin: relationship between toxicity and the induction of aryl hydrocarbon hydroxylase and ornithine decarboxylase

Both ornithine decarboxylase (ODC) and aryl hydrocarbon hydroxylase (AHH) are inducible by 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) in rodents. Moreover, in genetically inbred mice the induction of both enzymes appears to be mediated through the ligand-activated Ah receptor protein. In rats, there is a 6 hour peak of induced ODC activity which occurs after administration of high (250 ug/kg) but not low (1-100 ug/kg) doses of 2,3,7,8-TCDD; the 6 hour peak of activity is not observed at any other times points following exposure to the toxin. The induction of AHH is a time and dose-dependent process in which enzyme activity is maximized 72 hours after treatment with 2,3,7,8-TCDD and persists for several days. Coadministration of -difluoromethylornithine (DFMO) and a toxic dose of 2,3,7,8-TCDD (250 umol/kg) completely eliminated the induction of ODC but did not effect the induction of AHH or alter the toxicity (thymic atrophy) of 2,3,7,8-TCDD. These results confirm that both ODC and AHH are induced by 2,3,7,8-TCDD and that the induction of the former enzyme does not play a role in modulating AHH induction or thymic atrophy.