Ascorbic acid deficiency decreases specific forms of cytochrome P-450 in liver microsomes of guinea pigs.
Ascorbic acid (VC) deficiency resulted in a decrease in the activities of aminopyrine N-demethylase, aniline hydroxylase, and p-nitroanisole O-demethylase and in the content of cytochrome P-450, as spectrally determined, whereas it caused an increase in the activities of 6 beta-hydroxylases for testosterone and progesterone in liver microsomes of guinea pigs. Western blot analysis of liver microsomes with antibodies to rat P-448-H (P-4501A2), P-450j (P-450IIE), P-450 PB-1 (P-450IIIA), and P-450b (P-450IIB1) showed that VC deficiency decreased the amount of cytochrome P-450 immunochemically related to P-450IA2 and P-450IIE but did not change the amount of the form that was cross-reactive with antibodies to P-450IIB1 and tended to slightly increase (not statistically significantly) the amount of the form of the cytochrome immunochemically related to P-450IIIA. The larger decrease by VC deficiency in the amount of cytochrome P-450 that was cross-reactive to the rat P-450IA2 resulted in a lower capacity of liver microsomes to activate promutagens, such as 2-amino-3-methyl-imidazo(4,5-f)quinoline and aflatoxin B1. These results indicate that VC deficiency in guinea pigs differentially affects the content of individual forms of cytochrome P-450.
Kanazawa
Y
Y
Tenshi Junior College, Sapporo, Japan.
Kitada
M
M
Mori
T
T
Inukai
Y
Y
Imaoka
S
S
Funae
Y
Y
Kamataki
T
T
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000633:toxicity; D000818:Animals; D001206:Ascorbic Acid Deficiency / Q000201:enzymology*; D015153:Blotting, Western; D002273:Carcinogens / Q000633:toxicity; D019388:Cytochrome P-450 CYP1A2; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006168:Guinea Pigs; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D009245:NADH Dehydrogenase / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D011804:Quinolines / Q000633:toxicity
D000348:Aflatoxins; D002273:Carcinogens; D007527:Isoenzymes; D011804:Quinolines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1; D010088:Oxidoreductases; D019388:Cytochrome P-450 CYP1A2; D009245:NADH Dehydrogenase