Induction of enzymes by glucagon, glucose repression, adenosine 3',5'-monophosphate concentration during carcinogenesis and in Morris 6918A hepatoma.
We have studied glucagon induction of enzymes, adenosine 3', 5'-monophosphate concentrations, and glucose repression in Morris 9618A hepatoma and in the liver of rats fed, for periods of up to 5 weeks, a solid diet containing 2-acetylaminofluorene or 3'-methyl-4-dimethylaminoazobenzene. While the basal levels of the enzymes serine dehydratase and tyrosine aminotransferase were the same as those found in control rats, their response to glucagon was reduced in experimental animals with or without tumors. However, the basal or glucagon-stimulated levels of adenosine 3', 5'-monophosphate in the liver of rats given the carcinogens were not changed. In Morris 9618A hepatoma, these parameters were, likewise, comparable to those in control animals. When glucose was administered to carcinogen-treated or tumor-bearing rats that had received a single dose of glucagon, there was no suppression of the increase in activity of serine dehydratase and tyrosine aminotransferase observed after glucagon treatment alone. The loss of glucose repression was seen already at 2 to 3 weeks following initiation of the carcinogenic diets. As previous studies had established for normal liver, the hormone-induced high levels of adenosine 3',5'-monophosphate remained unchanged also in Morris 9618A hepatoma and in rats given carcinogen. These results indicate that alterations in enzyme induction during chemical carcinogenesis are not the consequence of changes in adenosine 3',5'-monophosphate levels caused by carcinogens. The early disappearance of the glucose effect, which persists in slow-growing hepatomas, may be an expression of interference by carcinogens with the translation apparatus of the hepatic cell.
D000818:Animals; D002273:Carcinogens; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D000242:Cyclic AMP / Q000378:metabolism*; D004790:Enzyme Induction; D004794:Enzyme Repression; D005449:Fluorenes; D005934:Glucagon / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D012695:L-Serine Dehydratase / Q000378:metabolism*; D008113:Liver Neoplasms / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D008297:Male; D009374:Neoplasms, Experimental / Q000201:enzymology / Q000473:pathology; D051381:Rats; D014444:Tyrosine Transaminase / Q000378:metabolism*
D002273:Carcinogens; D005449:Fluorenes; D005934:Glucagon; D000242:Cyclic AMP; D014444:Tyrosine Transaminase; D012695:L-Serine Dehydratase; D005947:Glucose