Molecular Pharmacology, Vol 8, 722-730, Copyright © 1972 by the American Society for Pharmacology and Experimental Therapeutics

The Conversion of Hepatic Cytochrome P-450 to P-420 in Normal and Phenobarbital- and 3-Methylcholanthrene-Treated Animals

¹ Department of Biochemistry, The University of Texas Southwestern Medical School at Dallas, Dallas Texas 75235

The conversion of rat and rabbit hepatic microsomal cytochrome P-450 to P-420 by mercurials does not proceed to completion. The percentage of cytochrome P-450 resistant to mercurial attack was greater in rats than in rabbits. It was increased by prior treatment with phenobarbital and decreased when the animals had been treated with 3-methylcholanthrene. Correlative studies using ethyl isocyanide as a ligand for reduced cytochrome P-450 instead of carbon monoxide demonstrated a loss of the 455 nm absorbance maximum in this difference spectrum, closely paralleling the loss of cytochrome P-450. The loss of the 455 nm absorbance maximum, however, did not always result in an increase in the absorbance maximum at 430 nm. The effect of low concentrations of mersalyl on the electron paramagnetic resonance spectrum at -172° of microsomes from 3-methylcholanthrene-treated animals suggests the presence of an undetectable form of cytochrome P-450. The differences in the susceptibility of cytochrome P-450 from different sources to mercurial degradation probably reflect changes in the whole population of cytochrome P-450 present in the microsomes.

Note:
ACKNOWLEDGMENTS The author thanks Mrs. Nancy J. Mahanay for her technical assistance, and Dr. Ronald W. Estabrook for his interest, encouragement, and advice.