POSTTRANSCRIPTIONAL ELEVATION OF CYTOCHROME-P450 3A EXPRESSION

Human CYP3A, the most abundant hepatic and intestinal cytochrome P450, catalyzes the metabolism of a diverse array of xenobiotics. Dimethyl sulfoxide is a commonly used solvent which has been used therapeutical ly. Dimethyl sulfoxide effects on CYP3A, CYP2E1, CYP2B and NADPH cytoc hrome P450 reductase expression in rat liver and in primary cultured r at hepatocytes were examined. Dimethyl sulfoxide increased immunodetec table hepatic CYP3A and CYP2E1 levels similar to 2.5 to 3-fold in the absence of any change in the respective mRNA levels. No change in CYP2 B or P450 reductase expression was observed, indicating that dimethyl sulfoxide effects were selective. Dimethyl sulfoxide also increased CY P3A protein in rats pretreated with dexamethasone. In primary cultured rat hepatocytes, dimethyl sulfoxide increased CYP3A and CYP2E1 protei n without increasing the respective mRNA levels. These results show th at dimethyl sulfoxide, at levels relevant to human exposure, enhances CYP3A and CYP2E1 expression by posttranscriptional mechanisms. (C) 199 7 Academic Press.