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The in vivo syntheses of two liver microsomal cytochromes P-450 PB 3a, P-450 UT 50[(1987) Eur. J. Biochem., submitted] ( Mr50 000, 52 000) have been estimated by measuring the specific activity 2 h after i.p. administration of δ-[ 3H]aminolevulinic acid to male Sprague Dawley rats. The animals were fed either a standard rat chow (5% lard, 22% casein) or unbalanced diets (high lipid, 30% lard or low protein, 6% casein) with or without 50 ppm Phenoclor DP6. The high-lipid diet supported a more rapid body weight gain but had little impact on cytochrome P-450 content, expressed either per whole liver or per mg microsomal protein, and on the incorporation of the precursor into cytochrome P-450. The latter was determined by measuring the radioactivity incorporated into the cytochrome P-450 fraction, partially purified by afffinity chromatography, as well as into two cytochrome P-450 isozymes ( Mr50 000 or 52 000) purified by DEAE-52 cellulose ion-exchange chromatography. The low-protein diet, on the other hand, severely depressed body weight gain and cytochrome P-450 content as well as incorporation of radioactivity, the lower- Mrcytochrome ( Mr50 000) being particularly affected. However, when a potent inducer, Phenoclor DP6, was added to the low-protein diet, cytochrome synthesis was restored indicating that the effect was reversible.