Inhibition of mitochondrial protein synthesis during early stages of aflatoxin B1-induced hepatocarcinogenesis.
Experiments were designed to determine the in vivo effects of a single 6-mg/kg dose aflatoxin B1 on rat liver mitochondrial transcription and translation processes. With the use of intact hepatocytes and also a highly active mitoplast system for incorporation, it was observed that both mitochondrial transcription and translation activities are inhibited progressively even after 24 hr of carcinogen administration. Electrophoretic patterns of mitochondrial translation products show some qualitative changes during early periods of carcinogen administration. At later stages (greater than 12 hr), however, there is a general inhibition of many of the products, although by this time there is a qualitative and quantitative recovery in the synthesis of mitochondrial proteins imported from the cytoplasm. These results, along with the data showing considerably high levels of aflatoxin B1 binding to mitochondrial DNA suggest that mitochondrial genetic system is one of the direct targets during experimental carcinogenesis.
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D011230:Precancerous Conditions / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000187:drug effects; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D014158:Transcription, Genetic / Q000187:drug effects
D000348:Aflatoxins; D012313:RNA; D004247:DNA; D016604:Aflatoxin B1