Apparent differential response of nuclear envelope cytochrome P-450 following phenobarbital induction arising from a preferential loss during gradient purification.

We have investigated the response of rat liver nuclear, nuclear envelope, and microsomal cytochrome P-450 (or P-448) to various treatments. Responses of these subcellular fractions to 3-methylcholanthrene pretreatment were generally similar. In endoplasmic reticulum preparations, we observed an increase in cytochrome P-450 content following phenobarbital pretreatment, which was reduced by subsequent thioacetamide treatment. Nuclear envelope cytochrome P-450 was apparently not modulated by these treatments, although nuclear cytochrome P-450 content was increased by phenobarbital. When endoplasmic reticulum preparations were subjected to treatments paralleling those used in nuclear envelope purification, we found a preferential loss of cytochrome P-450 from phenobarbital-pretreated preparations, with a loss of camphor-binding ability. The data point to potential problems with use of isolated nuclear envelopes as a representative model for nuclear metabolism of carcinogens, including low total recoveries and enrichments, and the potential for selective or differential recovery of cytochrome P-450 populations following various modes of induction or reduction.