Study of the relationship of nucleic acid and protein synthesis to mammalian enzyme induction
Rubin, Robert Jay
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The increase in activity of two hepatic enzymes, tryptophan pyrrolase and benzpyrene hydroxylase, following administration of their respective substrates, has been ascribed to de novo synthesis of protein. For this reason agents known to have profound effects on protein synthesis in other systems were investigated for their effect on induction of these two enzymes. Further, a study was made of the nucleic acid turnover during tryptophan pyrrolase induction. Finally, food deprivation was investigated for its effect on the two enzyme systems. Dimethylaminoazobenzene (DMAB) fed to adult rats at a level of 0.06% in the diet caused a progressive decrease in the basal level of tryptophan pyrrolase over a period of 42 days and a significant inhibition of the 5 hour-induced level of enzyme, evident as early as 14 days with no further changes seen as late as 42 days. After 240 days of feeding, the basal and induced enzyme levels appeared to return to control levels. There was seen markedly less enzyme activity in hepatic tumor tissue from induced rats than was found in the adjoining normal-appearing liver. DMAB, administered to rats in a single dose of 25 mg/100 gm body weight 24 hours before induction, had no significant effect on the basal or induced enzyme levels [TRUNCATED].
Thesis (Ph.D.)--Boston University.