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Apparent Differential Response of Nuclear Envelope Cytochrome P-450 following Phenobarbital Induction Arising from a Preferential Loss during Gradient Purification¹

Department of Pathology, University of California School of Medicine, San Francisco, California 94143

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.

¹ This investigation was supported by Grants CA21141 and AM19843 from the USPHS.

² To whom requests for reprints should be addressed, at Department of Pathology, HSW 547, University of California School of Medicine, San Francisco, Calif. 94143.

Received 12/ 4/80. Accepted 5/11/81.