A biochemical and electron microscopic study of changes in the content of cytochrome P-450 in rat livers after cessation of treatment with phenobarbital, .BETA.-naphtoflavone or 3-methylcholanthrene.

Abstract

Changes in rat livers after treatment with phenobarbital (PB), .beta.-naphthoflavone (.beta.NF) or 3-methylcholanthrene (MC) were investigated by biochemical, immunochemical and EM methods. Repeated injections of each drug led to increases in the relative liver weights, in the microsomal proteins/g liver, in the microsomal contents of the total cytochrome P-450 and in the corresponding molecular species of P-450 (P-450(PB), when treated with PB and P-450(MC) when treated with .beta.NF or MC). After cessation of treatment with PB or .beta.NF, decreases in all contents to essentially control values took place approximately in parallel within 7 days. The apparent half lives of cytochrome P-450(PB) and P-450(MC) were calculated from the regression lines of cytochrome P-450 as .apprx. 15 h. After treatment with MC, all increases were maintained at approximately the maximal values even after 9 days. EM revealed the smooth ER [endoplasmic reticulum], which markedly proliferated on PB or .beta.NF treatment, decreased rapidly after drug treatment stopped, and was accompanied by an increase in the number of autophagosomes. After treatment with MC, the proliferated smooth ER remained even after 9 days.