DNA damage in rodent liver by 1,2-dichloroethane, a hepatocarcinogen.

The transcriptional and replicative activities of hepatic nuclei during DNA damage induced by 1,2-dichloroethane (DCE), a hepatocarcinogen, were examined. DNA damage was measured by DNA alkylation in rodents exposed to DCE. A time-dependent DNA damage in vivo and in vitro was observed. A significant inhibition of RNA synthesis was observed when transcription was carried out in vitro using nuclei of DCE-treated animal. The inhibition in RNA synthesis persisted even when 50% of DNA damage was removed. Similarly, nuclear DNA synthesis in vitro was also significantly inhibited during DNA damage. However, DNA synthesis was recovered rapidly even though 50% of DNA damage persisted. Results on the effect of alpha-amanitin on RNA synthesis suggest that 50-70% of synthesis was carried out by RNA polymerase II.