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.
Banerjee
S
S
Department of Molecular Biology, Cleveland Clinic Foundation, OH 44195.
D000478:Alkylation; D000546:Amanitins / Q000494:pharmacology; D000818:Animals; D002273:Carcinogens; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication / Q000187:drug effects; D005025:Ethylene Dichlorides / Q000633:toxicity*; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity*; D008099:Liver / Q000378:metabolism; D008297:Male; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D014158:Transcription, Genetic / Q000187:drug effects
D000546:Amanitins; D002273:Carcinogens; D005025:Ethylene Dichlorides; D006843:Hydrocarbons, Chlorinated; C024565:ethylene dichloride; D012313:RNA