RT Journal Article SR Electronic T1 Differential Regulation of Individual Sulfotransferase Isoforms by Phenobarbital in Male Rat Liver JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 795 OP 801 VO 26 IS 8 A1 Melissa Runge-Morris A1 Kelly Rose A1 Charles N. Falany A1 Thomas A. Kocarek YR 1998 UL http://dmd.aspetjournals.org/content/26/8/795.abstract AB Xenobiotics that induce the cytochromes P450 also produce changes in rat hepatic sulfotransferase (SULT) gene expression. In the present study, male Sprague-Dawley rats were treated for 3 consecutive days with doses of phenobarbital (PB) that induce cytochrome P450 2B1/2 expression. The effects of PB treatment on hepatic aryl SULT (SULT1) and hydroxysteroid SULT (SULT2) mRNA and immunoreactive protein levels and on mRNA expression of individual SULT1 and SULT2 enzyme isoforms were characterized. PB suppressed SULT1A1 mRNA levels, increased the expression of the SULT-Dopa/tyrosine isoform, and did not produce significant changes in SULT1C1 and SULT1E2 mRNA expression. In rats injected with the highest test dose of PB (100 mg/kg), hepatic SULT1A1 mRNA levels were decreased to ∼42% of control levels and SULT-Dopa/tyrosine mRNA levels were increased to ∼417% of vehicle-treated control levels. Like the SULT1 subfamily, individual members of the SULT2 gene subfamily were differentially affected by PB treatment. PB (35, 80, and 100 mg/kg) suppressed SULT20/21 mRNA expression to ∼61, ∼30, and ∼41% of vehicle-treated control levels, respectively. In contrast, SULT60 mRNA levels were increased to ∼162% of control levels and SULT40/41 mRNA levels were increased to ∼416% of vehicle-treated control levels in rats treated with 100 mg/kg PB. These studies support a complex role for PB-mediated effects on the SULT multigene family in rat liver. Because individual SULT1 and SULT2 enzyme isoforms are known to metabolize a variety of potentially toxic substrates, varied responses to PB among members of the SULT multigene family might have important implications for xenobiotic hepatotoxicity. The American Society for Pharmacology and Experimental Therapeutics