Abstract
The rat Reuber H-4-II-E continuous cell line contains 4-methylumbelliferone-UDP-glucuronosyltransferase activity. This enzyme is induced 3- to 6-fold by polycyclic aromatic compounds such as benzo[a]pyrene, 3-methylcholanthrene, benz[a]anthracene and 2,3,7,8-tetrachlorodibenzo-p-dioxin, by phenobarbital, or by isoproterenol. Induction of the transferase by most compounds is maximal by 48 hours; however, upon treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin or 3-methylcholanthrene, the activity rises for at least 72 hours. Certain hydroxylated metabolities of benzo[a]pyrene, at the same concentration as used for benzo[a]pyrene, are shown to be inferior inducers of activity. Available hydroxylated metabolites of benzo[a]anthracene or 3-methyicholanthrene do not induce transferase activity. Combinations of a polycyclic aromatic compound and phenobarbital—at their optimal concentrations when added individually—cause additive induction of transferase activity whereas combinations of two polycyclic aromatic compounds do not cause greater activity than the best inducer alone. The induction of activity by the best inducer, 2,3,7,8-tetrachlorodibenzo-p-dioxin, is progressively inhibited by increasing concentrations of either actinomycin D or cycloheximide. In contrast, if cells are first exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin and cycloheximide for a period of time and then washed, treatment with actinomycin D causes an unusually rapid rise in transferase activity, as compared with that in cells transferred to control medium. The Reuber H-4-II-E cultures therefore contain a UDP-glucuronosyltransferase activity which is inducible by the three different classes of inducers already known to exist for monooxygenase activity in cell culture (2). Furthermore, substrates for UDP-glucuronosyltransferase(s) do not appear to function as very efficient inducers of the transferase activity.
- Copyright © 1979 by Academic Press, Inc.
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