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.