Transcriptional regulation of rat liver glutathione S-transferase genes by phenobarbital and 3-methylcholanthrene.

The relative rates of transcription of the rat liver glutathione S-transferase Ya-Yc and Yb genes were determined in purified liver nuclei isolated at different times after phenobarbital or 3-methylcholanthrene administration. The transcriptional rates of the Ya-Yc and Yb genes were elevated approximately fivefold 8 and 6 h, respectively, after phenobarbital administration. In contrast, the transcriptional rates of the Ya-Yc genes were elevated approximately eightfold at 16 h after 3-methylcholanthrene administration, whereas the transcriptional rates of the Yb genes were elevated approximately fivefold at 6 h after the administration of this xenobiotic. The elevation in transcriptional activity of the glutathione S-transferase genes is sufficient to account for the increase in glutathione S-transferase mRNA levels determined previously by RNA blot hybridization [C. B. Pickett, C. A. Telakowski-Hopkins, G. J-F. Ding, L. Argenbright, and A. Y. H. Lu (1984) J. Biol. Chem. 259, 5182-5188]. Therefore, it appears that phenobarbital and 3-methylcholanthrene elevate the level of the rat liver glutathione S-transferases primarily by augmenting the transcriptional rates of their respective genes.