Heteroactivation of Cytochrome P450 1A1 by Teas and Tea Polyphenols

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 2005 May 17

PMID 15895106

Citations 6

Authors

Dana L Anger

Maria-Alexandra Petre

Denis J Crankshaw

Affiliations

Soon will be listed here.

Abstract

We studied 7-ethoxyresorufin deethylase as an index of cytochrome P4501A1 (CYP1A1) activity in liver microsomes from rats pretreated with 3-methylcholanthrene. The enzyme had complex kinetics compatible with a multisite model. At 1 microM substrate, brewed black, green and white teas had complex effects on enzyme activity consisting of activation at low concentrations and inhibition at higher concentrations. Data fit well to a two-site model that allowed us to determine maximal activation (% increase above control), pEC(50) for activation (g ml(-1)) and pIC(50) for inhibition (g ml(-1)). These parameters were 190+/-40, 5.9+/-0.1 and 4.51+/-0.09 for green tea, 350+/-40, 5.43+/-0.05 and 5.43+/-0.05 for black tea and 230+/-80, 5.3+/-0.3 and 4.7+/-0.2 for white tea, respectively. The effects of the brewed teas were mimicked to different degrees by the green tea polyphenols. Maximal activation, pEC(50) (M) and pIC(50) (M) were: (-)-epicatechin, 55+/-9, 5.4+/-0.3, 2+/-1; (-)-epicatechin gallate, 160+/-60, 6.2+/-0.3, 5.28+/-0.06; (-)-epigallocatechin 30+/-10, 6.5+/-0.5, 3.37+/-0.08; and (-)-epigallocatechin gallate 130+/-40, 6.7+/-0.3, 5.0+/-0.1. A crude extract of black tea polyphenols inhibited 7-ethoxyresorufin deethylase, but did not cause enzyme activation consistently. Enzyme activation was dependent upon substrate concentration. Heteroactivation of CYP1A1 may partially explain the lack of agreement between biological and epidemiological evidence of a role for tea in cancer prevention.

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