Effects of dietary lipid and phenobarbitone on the distribution and concentration of cytochrome P-450 in the liver studied by quantitative cytochemistry.

Cytochrome P-450 is an important component of the NADPH-dependent electron-transport system located in the endoplasmic reticulum of liver parenchymal cells and is the terminal oxidase involved in the oxidative metabolism of drugs, anaesthetics, carcinogens, steroid hormones, insecticides, environmental pollutants and fatty acids. In the reduced form this haemoprotein binds carbon monoxide to produce a characteristic Soret absorption band at 450 nm and is therefore routinely assayed in the microsomal fraction by measuring the difference spectrum of reduced cytochrome P-450 in the presence and absence of Carbon monoxide [ 11. It is well established that phenobarbitone administration increases the concentration of cytochrome P-450 in liver microsomes [2,3], and that variations in the content and composition of the dietary lipid can also markedly affect the concentration of cytochrome Pd.50 in liver microsomes [4,5]. Quantitative cytochemical measurements of the concentration of cytochrome P-450 in small groups of cells located in unfixed tissue sections using a Zeiss Universal Microspectrophotometer (type I) have shown that cytochrome P-450 is not evenly distributed in rat liver and is induced selectively in the centrilobular hepatocytes by phenobarbitone [6,7]. The effects of changes in dietary li$d composition on the distribution of cytochrome P-450 within the rat liver lobule have not been investigated.