Retinoids inhibit 2,3,7,8-tetrachlorodibenzo-p-dioxine-induced activity of benzo[a]pyrene metabolizing enzymes in human diploid fibroblasts.

Retinoids are known to inhibit the substrate mediated enzyme induction of benzo[a]pyrene metabolizing enzymes. Consequently, the effect of two retinoids on the induction of benzo[a]pyrene metabolizing enzymes by the more potent inductor 2,3,7,8-tetrachlorodibenzo-p-dioxine (TCDD) was investigated. The studies were performed with human diploid fibroblasts in culture. Vitamin A palmitate and all-trans-retinoic-acid were found to prevent the TCDD induced increase of benzo[a]pyrene metabolism in a dose-dependent manner. The fact that this effect was immediately reversible makes it unlikely that it was due to non-specific toxic effects. The data suggest that retinoids cause a preferential inhibition of the de novo synthesis of benzo[a]pyrene metabolizing enzymes.