Induction of cytochrome P450 by xenobiotics.

It is apparent that the exposure of animals to xenobiotics has a profound effect upon the expression of cytochrome P450. In this manuscript, phenobarbital and 3MC have been selected from the many xenobiotics capable of eliciting this affect to demonstrate the magnitude of changes occurring at the level of the nucleic acids. We have seen that effects include increased levels of particular RNA polymerase isozymes; stabilization of ribosomes and increased synthesis of ribosomal RNA; increase in the amount of mature messenger RNA for individual cytochrome P450 components; and an increase in the amount of nuclear RNA precursors. How these effects come about is a matter for speculation. However, it is clear that the mechanisms by which this is accomplished differ substantially for both phenobarbital and 3MC. 3MC may induce cytochrome P450c through its interaction with a cytosolic "receptor" and subsequent activation of chromatin. The details must await further study.