Requirement of monooxygenase induction in cultured lung epithelial cells for metabolism of PAH

In vitro mammalian lung cell systems should mimic the cells of native organs as closely as possible. Particularly so, when the metabolic activity for PAH and other precarcinogens is studied. Although fetal (embryonic) cells have more proliferative capacity than adult ones in vitro, the fetal cells usually lack the induced enzyme activity for PAH metabolism. This may be one of the reasons why the fetal cells in culture need longer exposure periods for PAH activation when compared with freshly isolated adult cells. It appears that such potent inducers as benzo[a]pyrene and benz[a]anthracene enhance the level of CYP450 synthesis in the initial phase of exposure to an extent that this increased CYP450 subsequently can convert benzo[a]pyrene itself effectively. When phenanthrene, an incompetent inducer, is studied for its in vitro conversion, however, a pre-exposure of cells with potent monooxygenase inducers such as benzo[a]pyrene or benz[a]anthracene is required to attain sufficient levels of CYP450 for metabolizing phenanthrene. In addition, species-dependent differences in the induction of CYP450 by benzo[a]pyrene and benz[a]anthracene have been observed. This in vitro model may also be useful for the measurement of the inductive capacity of various xenobiotics for CYP450.