The genetic relationships and inducibility of soluble glutathione transferases of the rat liver.

extent were those obtained from cells treated with phenobarbital and dexamethasone; this indicated that the cytochrome P-450 found in these cells was similar to that found in adult rat liver (Fig. 2). This conclusion was also supported by results obtained after solubilization and chromatography on DEAE-cellulose of microsomes from these cells. As the experiments described above demonstrated that the mono-oxygenase development during the perinatal period was at least partially controlled by glucocorticoids, we decided to verify whether these hormones were responsible for a neonatal imprinting such as that described for sex steroids by Gustafsson et al. (1977). Cells were cultivated for 48 h in the presence of 0, 1 0 ~ ~ or 100mM-dexamethasone. The medium was then replaced by a fresh one containing or not dexamathasone and supplemented or not with phenobarbital. In cells which had not been treated with dexamethasone, aryl-hydrocarbon hydroxylase activity was inhibited by anaphthoflavone (Fig. 3). High concentrations of dexamethasone were needed to produce an inhibition by metyrapone and the disappearance of inhibition by a-naphthoflavone. Aryl-hydrocarbon hydroxylase activity was no longer inhibited by a-naphthoflavone when the cells were first treated with 100mMdexamethasone and then cultivated in the absence of the corticoid. Similarly, aldrin epoxidase was well induced in cells which had first been treated with dexamethasone for 48 h before phenobarbital treatment. These results indicate that pretreatment of the hepatocytes with dexamethasone for 48 h produced a qualitative change in these cells. Pretreatment of the cells with a minimal amount of glucocorticoid produced an irreversible expression of a cytochrome P-450 species which was induced by phenobarbital and inhibited by metyrapone. Glucocorticoids most likely acted as a switch and modified the ratio between the various forms of cytochrome P-450 that were synthesized by the primary foetal liver cells in culture. Our results may lead to several new applications for cell-culture models and confirm that primary foetal cells in culture may be an excellent model for studying the regulation of the cytochrome P-450-supported mono-oxygenases.