Multiplicity of cytochrome P-450 in primary fetal hepatocytes in culture

Abstract

Primary fetal rat hepatocytes in culture display different monooxygenase activities which can be induced by several chemical inducers. Until now, these hepatocytes were believed to produce only one single cytochrome P-450 species, namely the cytochrome P1-450 (or P-448). It now seems possible to induce other cytochrome P-450 species in these hepatocytes, providing that they receive an appropriate hormonal treatment. We have examined the effect of dexamethasone on the cytochrome P-450 type supporting different enzymic activities (aryl hydrocarbon hydroxylase, ethoxycoumarin deethylase, aldrin monooxygenase). Our results show that the presence of dexamethasone in the culture medium produces qualitative and quantitative changes in the monooxygenase-supporting cytochrome(s) P-450. For low dexamethasone concentrations (between 1 nM and 0.1 microM) a cytochrome P-450 is formed displaying biochemical and biophysical properties similar to those induced by phenobarbital in the adult rat liver. At higher concentrations (above 1 microM), similar qualitative changes are observed; but a quantitative phenomenon occurs, the (cytochrome P-450)-dependent enzymic activities being also induced. Dexamethasone also has a synergistic effect on the induction of enzymic activity by the mixture of phenobarbital plus benzanthracene. The various biochemical changes induced by dexamethasone in the fetal cell cultures parallel those observed in vivo during the perinatal period of life. The cell culture system may thus constitute an interesting model for studying the ontogenic development of liver monooxygenases.