2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated oxidative stress in CYP1A2 knockout (CYP1A2-/-) mice

The objective of the study was to compare alterations in indicators of oxid ative stress following 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure in cytochrome P4501A2 (CYP1A2) knockout mice and their parental lineage str ains (C57BL/6N and 129/Sv), This study will aid in determining the role, if any, of CYP1A2 in TCDD-mediated oxidative stress. Formation of-thiobarbitu ric acid-reactive substances (TBARS) as a measurement of lipid peroxidation , production of reactive oxygen species (ROS) via the in vitro reduction of cytochrome c in tissue homogenate, and changes in the biochemical antioxid ant glutathione were monitored to determine oxidative stress 7 days followi ng a single oral dose of 25 mu g TCDD/kg. TEARS, reduction of cytochrome c, and changes in glutathione demonstrated a similar response in CYP1A2 knock out and parental strains. These data suggest that CYP1A2 does not play a cr itical role in the acute oxidative stress response following TCDD exposure. (C) 1999 Academic Press.