title: Inhibitory activity of green and black tea in a free radical-generating system using 2-amino-3-methylimidazo[4,5-f]quinoline as substrate.
abstract: Green tea and black tea inhibit colon carcinogenesis in rats exposed to the cooked meat mutagen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). In the present investigation, green tea, black tea and (-)-epigallocatechin gallate (EGCG) were shown to block the production of oxygen free radicals derived from IQ in the presence of NADPH-cytochrome P450 reductase. In kinetic studies using IQ as the substrate and DMPO as a free radical spin trap, EGCG increased the K(m) of the reaction without altering Vmax, suggesting competitive enzyme inhibition (Ki = 9.96 microM). This was confirmed in spectrophotometric studies using cytochrome c as the substrate, in which EGCG acted as a competitive inhibitor of NADPH-cytochrome P450 reductase (Ki = 9.7 microM). These results suggest that the inhibitory activities of green tea and black tea in electron spin resonance assays using IQ as the substrate for the reductase are related to an indirect effect on the enzyme rather than via direct scavenging of the free radicals. The possible implications of these findings are discussed in the context of pathways involved in the activation and detoxification of IQ in the colon.
authors.affiliation: Department of Surgery, University of Hawaii, Honolulu 96822, USA.
authors.forename: N
authors.initials: N
authors.lastname: Hasaniya
authors.forename: K
authors.initials: K
authors.lastname: Youn
authors.forename: M
authors.initials: M
authors.lastname: Xu
authors.forename: J
authors.initials: J
authors.lastname: Hernaez
authors.forename: R
authors.initials: R
authors.lastname: Dashwood
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents; D002392:Catechin / Q000031:analogs & derivatives*; D002851:Chromatography, High Pressure Liquid; D003110:Colonic Neoplasms / Q000517:prevention & control; D003497:Cyclic N-Oxides; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D007700:Kinetics; D008460:Meat; D009153:Mutagens / Q000737:chemistry*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D011804:Quinolines / Q000737:chemistry*; D051381:Rats; D013113:Spin Labels; D013662:Tea
chemical_list: D016588:Anticarcinogenic Agents; D003497:Cyclic N-Oxides; D005609:Free Radicals; D009153:Mutagens; D011804:Quinolines; D013113:Spin Labels; D013662:Tea; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; C017245:5,5-dimethyl-1-pyrroline-1-oxide; D002392:Catechin; C045651:epigallocatechin gallate; D009251:NADPH-Ferrihemoprotein Reductase