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 oxidative stress following 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure in cytochrome P4501A2 (CYP1A2) knockout mice and their parental lineage strains (C57BL/6N and 129/Sv). This study will aid in determining the role, if any, of CYP1A2 in TCDD-mediated oxidative stress. Formation of thiobarbituric 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 antioxidant glutathione were monitored to determine oxidative stress 7 days following a single oral dose of 25 microg TCDD/kg. TBARS, reduction of cytochrome c, and changes in glutathione demonstrated a similar response in CYP1A2 knockout and parental strains. These data suggest that CYP1A2 does not play a critical role in the acute oxidative stress response following TCDD exposure.
Slezak
B P
BP
Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Diliberto
J J
JJ
Birnbaum
L S
LS
D000818:Animals; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics*; D003574:Cytochrome c Group / Q000378:metabolism; D004785:Environmental Pollutants / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000235:genetics*; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors
D003574:Cytochrome c Group; D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D019388:Cytochrome P-450 CYP1A2; D005978:Glutathione