SUPERINDUCTION OF 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN-INDUCIBLE EXPRESSION OF ALDEHYDE DEHYDROGENASE BY THE INHIBITION OF PROTEIN-SYNTHESIS

Inhibition of protein synthesis by cycloheximide or puromycin super-induced the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible isoform of aldehyde dehydrogenase (ALDH-3) in rat hepatoma cells. Treatment with cycloheximide did not affect the basal expression but markedly enhanced the TCDD-inducible expression of ALDH-3 mRNA. The co-treatment of cycloheximide and TCDD for 24 h caused a 10-fold greater accumulation of ALDH-3 mRNA than did TCDD alone. The transcription rate of the ALDH-3 gene in the co-treated cells was also 4- to 5-fold higher than that in the cells treated with TCDD alone. The superinduction of ALDH-3 mRNA was observed only when cycloheximide was added prior to or simultaneously with the addition of TCDD. These results suggest that the mechanism of TCDD-inducible transcription of the ALDH-3 gene involves a labile protein that modulates or represses the action of TCDD. © 1991 Academic Press, Inc.