Constitutive androstane receptor -null mice are sensitive to the toxic effects of parathion: association with reduced cytochrome p450-mediated parathion metabolism [corrected].

ABSTRACT: Constitutive androstane receptor [corrected](CAR) is activated by several chemicals and in turn regulates multiple detoxification genes. Our research demonstrates that parathion is one of the most potent, environmentally relevant CAR activators with an EC(50) of 1.43 microM. Therefore, animal studies were conducted to determine whether CAR was activated by parathion in vivo. Surprisingly, CAR-null mice, but not wild-type (WT) mice, showed significant parathion-induced toxicity. However, parathion did not induce Cyp2b expression, suggesting that parathion is not a CAR activator in vivo, presumably because of its short half-life. CAR expression is also associated with the expression of several drug-metabolizing cytochromes P450 (P450). CAR-null mice demonstrate lower expression of Cyp2b9, Cy

SUBMITTER: Mota LC 

PROVIDER: S-EPMC2939475 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature