Effects of citrus flavonoids on the mutagenicity of heterocyclic amines and on cytochrome P450 1A2 activity.
Heterocyclic amines (HCA's) are promutagens produced by high temperature cooking of meat products and are activated by cytochrome P450 (CYP) lA2. Using Aroclor 1254 induced rat liver S9 we tested four citrus flavonoids diosmin, naringenin, naringin and rutin for their effects on the mutagenicity of HCA's MeIQx, Glu-P-1*, IQ and PhIP in Salmonella typhimurium TA98. The effects of the citrus flavonoids on CYPlA2 activity was determined by measuring demethylation of methoxyresorufin (MROD). MeIQx induced mutagenesis in S. typhimurium was significantly inhibited by all four flavonoids in a concentration dependent manner at 0.25, 0.5 and 1.0 mumole. Glu-P-1 induced mutagenesis was inhibited by rutin and naringenin. IQ induced mutagenesis was significantly inhibited by each flavonoid except diosmin at all three doses. With the exception of diosmin and naringin at 0.25 mumole all four flavonoids at all three doses significantly inhibited PhlP induced mutagenesis. The inhibition of MROD activity by the citrus flavonoids correlated best with the inhibition of MeIQx induced mutagenesis but also correlated with the inhibition of IQ induced mutagenesis except for diosmin and with the inhibition of PhlP induced mutagenesis except for the 0.25 mumole dose of diosmin and naringin. Our data suggest a chemopreventive potential for diosmin, naringin, naringenin and rutin towards CYPlA2 mediated mutagenesis of HCA's.
Bear
W L
WL
Department of Physiology and Pharmacology, Loma Linda University, School of Medicine, Loma Linda, CA 92350, USA.
Teel
R W
RW
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D016587:Antimutagenic Agents / Q000494:pharmacology*; D020111:Chlorodiphenyl (54% Chlorine) / Q000494:pharmacology; D002957:Citrus / Q000737:chemistry; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004145:Diosmin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D044950:Flavanones; D005419:Flavonoids / Q000494:pharmacology*; D007093:Imidazoles / Q000037:antagonists & inhibitors* / Q000633:toxicity; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011804:Quinolines / Q000037:antagonists & inhibitors / Q000633:toxicity; D011810:Quinoxalines / Q000037:antagonists & inhibitors / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D000091243:Ribosomal Protein S9; D012269:Ribosomal Proteins / Q000096:biosynthesis; D012431:Rutin / Q000494:pharmacology
D016588:Anticarcinogenic Agents; D016587:Antimutagenic Agents; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D044950:Flavanones; D005419:Flavonoids; D007093:Imidazoles; D009153:Mutagens; D011804:Quinolines; D011810:Quinoxalines; D000091243:Ribosomal Protein S9; D012269:Ribosomal Proteins; D020111:Chlorodiphenyl (54% Chlorine); C029216:2-amino-3-methylimidazo(4,5-f)quinoline; D012431:Rutin; C023785:2-amino-6-methyldipyrido(1,2-a-3',2'-d)imidazole; C036990:2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline; D004145:Diosmin; D003577:Cytochrome P-450 Enzyme System; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D010088:Oxidoreductases; C076307:methoxyresorufin-O-demethylase; D019388:Cytochrome P-450 CYP1A2; C005273:naringenin; C005274:naringin