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2,3,7, 8-TETRACHLORODIBENZO-P-DIOXIN (TCDD)-MEDIATED OXIDATIVE STRESS IN FEMALE CYP1A-2 KNOCKOUT (CYP1A2-/-) MICE
Citation:
Burgin, D. E., J J. Diliberto, AND L S. Birnbaum. 2,3,7, 8-TETRACHLORODIBENZO-P-DIOXIN (TCDD)-MEDIATED OXIDATIVE STRESS IN FEMALE CYP1A-2 KNOCKOUT (CYP1A2-/-) MICE. Presented at Society of Toxicology, San Francisco, CA, March 25-29,2001.
Description:
2,3,7,8-Tetrachlordibenzo-p-dioxin (TCDD)-Mediated Oxidative Stress in Female CYP1A2 Knockout (CYP1A2-/-) Mice
Deborah Burgin1, Janet Diliberto2, Linda Birnbaum2
1UNC Toxicology; 2USEPA/ORD/NHEERL, RTP, NC
Most of the effects due to TCDD exposure are mediated via the aryl hydrocarbon (Ah) receptor. Binding of TCDD to the Ah receptor leads to biological and toxic responses including dermal, immunotoxic, hepatotoxic, carcinogenic, teratogenic, neurobehavioral, endocrine, and metabolic alterations. An additional response under investigation is oxidative stress resulting from exposure to TCDD, which has been shown to increase the production of reactive oxygen species, lipid peroxidation and DNA damage. CYP1A1 and CYP1A2, members of the Ah gene battery and inducible with TCDD exposure, have been proposed to be associated with TCDD-mediated oxidative stress. Previous studies from this lab (Slezak et al, BBRC, 264, 1999) indicated that CYP1A2 did not play a role in acute induction of oxidative stress by TCDD in males. The objective of this study was to compare the oxidative damage induced by TCDD in CYP1A2 -/- female. Female C57Bl/6N (C57) and CYP1A2-/- mice were dosed with 25 ug TCDD/kg body weight at a dosing volume of 10 ml/kg and euthanized 7 days later. Markers of oxidative stress were measured in both liver and brain. There was no effect of TCDD on glutathione or uric acid levels in liver or brain in either strain. In contrast, TCDD led to an increase in hepatic ascorbate levels in the C57 females, but no effect was seen in the 1A2-/- females. This suggests a role of CYP1A2 in mediation of TCDD-induced oxidative stress in female mice. (This abstract does not necessarily represent EPA policy. This research was supported by EPA CT902908)