Monooxygenase and UDP-glucuronyltransferase activities in established cell culture

Cells in culture were investigated for the expression of monooxygenase and UDP-glucuronyltransferase activities as representatives of activating and inactivating pathways of drug metabolism. Most established cell lines express monooxygenase activity that is detected by the oxygenation of polycyclic hydrocarbons and appears to be a function of cytochrome P-448-dependent enzyme forms (Wiebel et al., 1977). In the hepatoma cell line, H-4-II-3, dexamethasone is capable of increasing the level of benzo(a)pyrene-monooxygenation about 10-fold and of potentiating its induction by benzo(a)anthracene. The enzyme activities elicited by dexamethasone and the polycyclic hydrocarbon did not significantly differ in their response to 7,8-benzoflavone, an inhibitor of cytochrome P-448-dependent monooxygenases. Observations on the pattern of benzo(a)pyrene metabolites formed in benz(a)anthracene-treated H-4-II-E and BHK21(C13) cells indicate that established cell cultures may contain different forms of monooxygenases of the cytochrome P-448 type. The majority of cell lines tested express UDP-glucuronyltransferase activity directed toward the substrate, 3-hydroxybenzo(a)pyrene. No clear correlation appears to exist between the presence and level of monooxygenase and glucuronyltransferase activities in the various cell lines, i.e., the cultures may express any one or both enzymes. The ratio of the two enzyme levels can be modified by selective induction. Thus, at present there is a choice of established cells in culture exhibiting widely differing ratios of activating and inactivating enzymes to analyse the metabolic pathways of selected classes of foreign compounds, such as polycyclic hydrocarbons, and to determine their toxicological significance. Further efforts are likely to yield cell lines that express the enzymic functions lacking in the cultures currently used and will be suitable to study the full spectrum of foreign compounds.