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RECORD NUMBER: 33 OF 135

Main Title Dose-Response Relationships in Mice Following Subchronic Exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin: CYP1A1, CYP1A2, Estrogen Receptor, and Protein Tyrosine Phosphorylation.
Author DeVito, M. J. ; Ma, X. ; Babish, J. G. ; Menache, M. ; Birnbaum., L. S. ;
CORP Author North Carolina Univ. at Chapel Hill. Center for Environmental Medicine and Lung Biology. ;Paracelsian, Inc., Ithaca, NY. Cellular Physiology Section. ;New York State Coll. of Veterinary Medicine, Ithaca. ;Duke Univ. Medical Center, Durham, NC. Center for Extrapolation Modelling.;Health Effects Research Lab., Research Triangle Park, NC. Environmental Toxicology Div.
Publisher c1994
Year Published 1994
Report Number EPA-R-817643 ;EPA-R-813113; EPA/600/J-94/196;
Stock Number PB94-163755
Additional Subjects Tetrachlorodibenzodioxin ; Toxicity ; Cytochrome P-450 ; Estrogen receptors ; Tyrosine ; Dose-response relationships ; Phosphorylation ; Liver ; Lung ; Skin(Anatomy) ; Reprint ;
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NTIS  PB94-163755 Some EPA libraries have a fiche copy filed under the call number shown. 07/26/2022
Collation 10p
Abstract
The dose-response relationships for different endpoints in different tissues were compared in response to 2,3,7,8-tetrachlorodibenzodioxin (TCDD) treatment. TCDD was administered 5 days/week for 13 weeks at doses ranging from 1.5 - 150 ng/kg/day to female B6C3F1 mice. Ethoxyresorufin-O-deethylase (EROD) activity was increased in liver, lung and skin at doses as low as 1.5 ng/kg/day. EROD activity did not attain maximal induction. Liver acetanilide-4-hydroxylase activity was induced at doses as low as 1.5 ng/kg/d and reached maximal induction at 45 ng/kg/d. TCDD treatment significantly increased the amount of three phosphotyrosyl proteins in liver S-20 fractions. Changes in phosphotyrosyl proteins reached maximal induction at 4.5 ng/kg/d. Hepatic and uterine estrogen receptor levels were unchanged at any of the doses tested. These data indicate that TCDD produces multiple effects with multiple dose-response curves suggesting that there are events in addition to receptor binding that are endpoint-specific, leading to different dose-response relationships.