DIFFERENTIAL REGULATION OF INDIVIDUAL SULFOTRANSFERASE ISOFORMS BY PHENOBARBITAL IN MALE-RAT LIVER

Xenobiotics that induce the cytochromes P450 also produce changes in r at hepatic sulfotransferase (SULT) gene expression. In the present stu dy, male Sprague-Dawley rats were treated for 3 consecutive days with doses of phenobarbital (PB) that induce cytochrome P450 2B1/2 expressi on, The effects of PB treatment on hepatic aryl SULT (SULT1) and hydro xysteroid SULT (SULT2) mRNA and immunoreactive protein levels and on m RNA expression of individual SULT1 and SULT2 enzyme isoforms were char acterized, PB suppressed SULT1A1 mRNA levels, increased the expression of the SULT-Dopa/tyrosine isoform, and did not produce significant ch anges in SULT1C1 and SULT1E2 mRNA expression. In rats injected with th e highest test dose of PB (100 mg/kg), hepatic SULT1A1 mRNA levels wer e decreased to similar to 42% of control levels and SULT-Dopa/tyrosine mRNA levels were increased to similar to 417% of vehicle-treated cont rol levels, Like the SULT1 subfamily, individual members of the SULT2 gene subfamily were differentially affected by PB treatment. PB (35, 8 0, and 100 mg/kg) suppressed SULT20/21 mRNA expression to similar to 6 1, similar to 30, and similar to 41% of vehicle-treated control levels , respectively, In contrast, SULT60 mRNA levels were increased to simi lar to 162% of control levels and SULT40/41 mRNA levels were increased to similar to 416% of vehicle-treated control levels in rats treated with 100 mg/kg PB, These studies support a complex role for PB-mediate d effects on the SULT multigene family in rat liver, Because individua l 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 xenob iotic hepatotoxicity.