The effect of ellagic acid on xenobiotic metabolism by cytochrome P-450IIE1 and nitrosodimethylamine mutagenicity.
Ellagic acid (EA) is an inhibitor of the in vitro mutagenicity of N-nitrosodimethylamine (NDMA) in Salmonella typhimurium strain TA100 using pyrazole-induced rat liver 9000 x g supernatant (S-9). In order to understand this activity, the effect of EA on the metabolic hydroxylation of 4-nitrophenol, a substrate, as is NDMA, for cytochrome P-450IIE1 was studied using pyrazole induced rat S-9 and microsomal protein. It is shown that EA has an inhibitory effect on 4-nitrophenol hydroxylase with both enzyme preparations. This effect on cytochrome P-450IIE1 may be responsible, at least in part, for the inhibition of NDMA mutagenicity by EA.
Wilson
T
T
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha 68198-6805.
Lewis
M J
MJ
Cha
K L
KL
Gold
B
B
D000818:Animals; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004128:Dimethylnitrosamine / Q000633:toxicity*; D004610:Ellagic Acid / Q000494:pharmacology*; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism*; D051381:Rats; D012486:Salmonella typhimurium / Q000235:genetics; D015262:Xenobiotics / Q000378:metabolism*
D009153:Mutagens; D015262:Xenobiotics; D004610:Ellagic Acid; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating; D004128:Dimethylnitrosamine; D004121:Dimethyl Sulfoxide