Initiation of transcription in nuclei is inhibited by captan

Captan (N-trichloromethylthio-4-cyclohexene-1,2-dicarboximide) was examined for its effects on bovine liver nuclear RNA synthesis. Transcription was measured by [3H] UTP incorporation into either acid insoluble product or isolated RNA. Captan (1 mM) was found to inhibit RNA synthesis 50% in intact nuclei and 70% in a hypotonic lysate of nuclei. Individual RNA polymerase activities were distinguished in both intact nuclei and hypotonic lysate by alpha-amanitin sensitivity. Captan inhibited RNA polymerase I and II activities to an equal extent in both intact and lysate systems. The sulfhydryl compound dithiothreitol (DTT) protected the RNA polymerase activities from inhibition by captan. Initiation of transcription in intact nuclei was measured by [gamma-32P] ATP incorporation into purified RNA and was found to be inhibited 75% by 1 mM captan. This report describes the inhibition of nuclear RNA polymerase activities by captan and suggests a possible mechanism for its toxic effect on eukaryotic polymerases.