title: Modulation of hepatic transcription and translation during early stages of aflatoxin B1 carcinogenesis.
abstract: Isolated rat hepatocytes have been used to study the transcription and translation processes at varied time intervals after administration of a single dose (6 mg/kg) of hepatocarcinogen aflatoxin B1 (AFB1). The effects of AFB1 during the first 24 h of drug treatment show a characteristic inhibition followed by periods of rapid recovery and also a hyperactive state when both heterogeneous nuclear RNA (HnRNA) transcription and cytoplasmic translation processes reach about 200% of control. Analysis of [3H]orotic acid pulse-labeled HnRNA and cytoplasmic polyadenylic acid(poly (A)) containing mRNA on sucrose gradients under conditions which prevent aggregation show a stepwise reduction in the total isotopic incorporation as well as in the size distribution during the first 9 h of AFB1 treatment. Between 9 and 24 h after AFB1 treatment, there is a recovery in the total incorporation as well as in the size of HnRNA and poly (A) containing mRNA. Analysis of translation products by a two-dimensional procedure shows loss of some high molecular weight products in AFB1-treated cells. At 24 h after AFB1 treatment (hyperactive stage) there is a total recovery of activity. Also, several new translation products not detected in the control hepatocytes are synthesized at this stage. The hyperactive stage might represent gene-derepression or reprogramming of gene expression.
mesh_terms: D016604:Aflatoxin B1; D000348:Aflatoxins / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism*; D008297:Male; D014176:Protein Biosynthesis / Q000187:drug effects*; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D000348:Aflatoxins; D002273:Carcinogens; D012313:RNA; D016604:Aflatoxin B1