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.
Kohl
F V
FV
University of Hamburg, I. Medizinische Klinik, GFR.
Rüdiger
H W
HW
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001564:Benzo(a)pyrene / Q000378:metabolism*; D002478:Cells, Cultured; D004147:Dioxins / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004171:Diploidy; D004224:Diterpenes; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology*; D006801:Humans; D000084562:Retinyl Esters; D012867:Skin / Q000166:cytology; D012995:Solubility; D014212:Tretinoin / Q000494:pharmacology*; D014316:Tritium; D014801:Vitamin A / Q000031:analogs & derivatives* / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D004147:Dioxins; D004224:Diterpenes; D000084562:Retinyl Esters; C066841:2,3,7,8-tetrabromodibenzo-4-dioxin; D014316:Tritium; D014801:Vitamin A; C014794:retinol palmitate; D001564:Benzo(a)pyrene; D014212:Tretinoin