TY - JOUR
T1 - 2,3,7,8-Tetrachlorodibenzo-p-dioxin
T2 - relationship between toxicity and the induction of aryl hydrocarbon hydroxylase and ornithine decarboxylase
AU - Farrell, K.
AU - Safe, S.
N1 - Funding Information:
The financial assistance of the Texas Agricultural Experiment Station and the National Institutes of Health is appreciated. We also thank S. Bandiera, S. Lovering and B. Zmudzka for their invaluable assistance.
Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 1986
Y1 - 1986
N2 - 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.
AB - 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.
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U2 - 10.1016/0045-6535(86)90494-7
DO - 10.1016/0045-6535(86)90494-7
M3 - Article
AN - SCOPUS:0022911002
SN - 0045-6535
VL - 15
SP - 1971
EP - 1976
JO - Chemosphere
JF - Chemosphere
IS - 9-12
ER -