The ratio of two isozyme groups in microsomal cytochrome P-450 under exogenous influence of carbon tetrachloride and cyclophosphamide.
A method for measuring the content of two groups of microsomal cytochrome P-450 isozymes--cytochromes P-450W and P-450L--with the active sites directed into the water phase and membrane lipids, respectively, has been developed. The method is based on the ability of the xanthine oxidase-menadione complex to reduce microsomal cytochromes b5 and P-450 under anaerobic conditions by transferring electrons to hemoproteins with the active sites directed into the water phase. Cytochrome b5 is completely reduced (to the dithionite level) and cytochrome P-450 is reduced partially (only a group of cytochromes P-450W). The amount of cytochromes P-450L is estimated using the difference between the total content of cytochrome P-450 reduced by sodium dithionite and the content of cytochromes P-450W. The possibility of controlling the ratio of these two isozyme groups in cytochrome P-450 in vivo in membranes of the endoplasmic reticulum by pretreatment of animals with a variety of chemicals has been demonstrated. The ratio of cytochromes P-450W and P-450L has been shown to decrease two-fold 18 days after three injections of phenobarbital into mice. Carbon tetrachloride and cyclophosphamide also decrease this ratio in vivo.
Izotov
M V
MV
Institute of Applied Molecular Biology, Moscow, USSR.
Shcherbakov
V M
VM
Devichensky
V M
VM
Spiridonova
S M
SM
Lugovaja
L V
LV
Benediktova
S A
SA
D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity*; D003520:Cyclophosphamide / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis*; D007527:Isoenzymes / Q000032:analysis*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains
D007527:Isoenzymes; D003520:Cyclophosphamide; D003577:Cytochrome P-450 Enzyme System; D002251:Carbon Tetrachloride; D010634:Phenobarbital