Comparison of White Tea, Green Tea, Epigallocatechin-3-Gallate, and Caffeine as Inhibitors of PhIP-Induced Colonic Aberrant Crypts

Abstract:

There is growing interest in the possible health benefits of tea. We reported previously on the inhibition by white tea of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced colonic aberrant crypt foci (ACF) in the rat (4). To distinguish between blocking and suppressing effects, and thus provide mechanistic insights into prevention during the initiation versus post-initiation phases of carcinogenesis, white tea, and green tea were administered at 2% (w/v) as the sole source of drinking fluid either 2 wk before and 2 wk during PhIP dosing (100 mg/kg, every other day by oral gavage), or starting 1 wk after the carcinogen and continued until the study was terminated at 16 wk. In the former protocol, each tea produced marginal inhibition of colonic ACF, despite evidence for changes in several hepatic enzymes involved in heterocyclic amine metabolism. Post-initiation, however, the data were as follows (ACF/colon, mean ± SE): PhIP/water 12.2 ± 1.5; PhIP/white tea 5.9 ± 0.9 (∗∗ P < 0.01); PhIP/caffeine 5.9 ± 1.5 (∗∗ P < 0.01); PhIP/EGCG 3.5 ± 0.8 (∗∗∗P < 0.001); PhIP/green tea 8.9 ± 1.2 (P = 0.22, not significant). In the latter study, apoptosis was determined using in situ oligo ligation and cleaved caspase-3 assays, whereas cell proliferation was assessed via bromodeoxyuridine (BrdU) incorporation. No consistent changes were seen in apoptosis assays, but BrdU labeling was as follows (percent of cells positive/colonic crypt, mean ± SE): PhIP/water 10.4 ± 0.6; PhIP/white tea 8.6 ± 0.2 (∗P < 0.05); PhIP/EGCG 6.0 ± 0.85 (∗∗ P < 0.01); PhIP/caffeine 8.75 ± 0.45 (∗P < 0.05); PhIP/green tea 9.5 ± 0.4 (P > 0.05, not significant). The data imply that white tea, caffeine, and EGCG may be most effective post-initiation, via the inhibition of cell proliferation in the colon and through the suppression of early lesions.

Acknowledgments and Notes

We thank C. Riegger of DSM Nutritional Products for providing EGCG (TEAVIGO^TM), and Q. Li, T.-W. Yu, M.C. Myzak, P. Tong, V. Elias, M. Moussaoui, and M. Louderback for assistance during necropsy. Laboratory Animal Service staff are gratefully acknowledged for help with animal care. We dedicate this work to the memory of Joy Edlund (Stash Tea Co., Portland, OR), who was instrumental in arranging for the supply of tea. This study was supported in part by NIH grants CA90890, CA65525, and CA80176, and by Inko's White Tea (New York, NY).