Polypeptide patterns of hepatic microsomes from Long-Evans rats treated with different xenobiotics

Two-dimensional gel electrophoresis was used to analyze hepatic microsomal polypeptides after treatment of immature, male Long-Evans rats with 3-methylcholanthrene, pregnenolone-16 alpha-carbonitrile, isosafrole, SKF-525A, Aroclor-1254, gamma-chlordane, or trans-stilbene oxide. Epoxide hydrolase and cytochromes P-450a, P-450bLE, P-450c, P-450d, and P-450e were all identified as resolved polypeptides in these electrophoretograms. Idiosyncratic polypeptide patterns characterized the microsomal preparations following treatment of rats with each inducing agent. Immunochemically identical cytochromes P-450bLE and P-450e were always present at the same relative levels even though their total amount varied 3-fold after induction by isosafrole, SKF-525A, Aroclor-1254, gamma-chlordane, and trans-stilbene oxide. Cytochromes P-450c and P-450d were coinduced by 3-methylcholanthrene, isosafrole, and Aroclor-1254, but their relative amounts varied. Pregnenolone-16 alpha-carbonitrile treatment resulted in an increase of a single major microsomal polypeptide which was also induced by phenobarbital, isosafrole, SKF-525A, Aroclor-1254, and trans-stilbene oxide. Only one polypeptide was identified as epoxide hydrolase in all of the microsomes analyzed. The results suggest that the levels of cytochromes P-450bLE and P-450e may be subject to coordinate control, whereas the other cytochromes P-450 are independently regulated.