Heteroactivation of cytochrome P450 1A1 by teas and tea polyphenols

1 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. 2 At 1  μ M substrate, brewed black, green and white teas had complex effects on enzyme activity consisting of activation at low concentrations and inhibition at higher concentrations. 3 Data fit well to a two‐site model that allowed us to determine maximal activation (% increase above control), p EC 50 for activation (g ml −1 ) and p IC 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. 4 The effects of the brewed teas were mimicked to different degrees by the green tea polyphenols. Maximal activation, p EC 50 ( M ) and p IC 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. 5 Enzyme activation was dependent upon substrate concentration. 6 Heteroactivation of CYP1A1 may partially explain the lack of agreement between biological and epidemiological evidence of a role for tea in cancer prevention.British Journal of Pharmacology (2005) 145 , 926–933. doi: 10.1038/sj.bjp.0706255