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• W1503373722 abstract "Abstract Compared with the induction process by benz[a]anthracene, aryl hydrocarbon hydroxylase induction in fetal rat hepatocyte cultures by phenobarbital is more sensitive to low doses of either actinomycin D or cycloheximide. When actinomycin D at 0.4 nm levels is added simultaneously with phenobarbital in the growth medium, the rate at which induced oxygenase activity accumulates is decreased by more than 30% of normal; this level of actinomycin D does not appreciably alter the enzyme induction by benz[a]anthracene. Stimulation of the oxidase activity by phenobarbital is blocked more than 90% when 35 nm cycloheximide is added with the inducer, whereas the induction process by benz[a]anthracene is unaffected with this level of inhibitor. By extrapolation to other studies in vivo and in cell culture, nucleolar synthesis of ribosomal RNA may be of more importance in the process of microsomal enzyme induction by phenobarbital than that by benz[a]anthracene. Degradation of the phenobarbital- or benz[a]anthracene-induced hydroxylase activity is the same whether the enzyme system is maximally or half-maximally induced; the half-life is 10.5 ± 3.6 hours in fresh control medium and 8.5 ± 2.5 hours in the presence of high levels of cycloheximide. Actinomycin D stabilizes or slightly stimulates the enzyme activity in fetal liver cells previously treated with either phenobarbital or benz[a]anthracene. The continued presence of either inducer in hepatocytes exposed to high levels of cycloheximide or actinomycin D also stabilizes the phenobarbital- or benz[a]anthracene-induced hydroxylase activity. Actinomycin D does not prevent the induction of oxidase activity in cells previously treated with cycloheximide and either inducer. Thus, the induction of aryl hydrocarbon hydroxylase activity by either phenobarbital or benz[a]anthracene requires RNA and protein synthesis initially and protein synthesis continuously, and subsequently is insensitive to actinomycin D for several hours. We therefore feel that the primary action of phenobarbital, like that of benz[a]anthracene, is at the level of transcription and that with either inducer there is also a secondary effect of lesser importance at the post-translational level in which the normal rate of decay of the induced enzyme is delayed." @default.
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• W1503373722 date "1971-09-01" @default.
• W1503373722 modified "2023-10-11" @default.
• W1503373722 title "Aryl Hydrocarbon Hydroxylase Induction in Mammalian Liver Cell Culture" @default.
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• W1503373722 doi "https://doi.org/10.1016/s0021-9258(18)61894-0" @default.
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