Carcinogenesis Advance Access published online on February 17, 2008
Carcinogenesis, doi:10.1093/carcin/bgn051
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Protective versus promotional effects of white tea and caffeine on PhIP-induced tumorigenesis and β-catenin expression in the rat
1 Linus Pauling Institute, Oregon State University, Corvallis OR 97331 USA
2 College of Veterinary Medicine, Oregon State University, Corvallis OR 97331 USA
3 Department of Statistics, Oregon State University, Corvallis OR 97331 USA
4 Biochemistry Division, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan
5 Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis OR 97331, USA
* To whom correspondence should be addressed at Linus Pauling Institute, Oregon State University, Corvallis, OR 97331-6512, USA. Tel: +541 737 5086; Fax: +541 737 5077; Email Rod.Dashwood{at}oregonstate.edu
A one-year carcinogenicity bioassay was conducted in rats treated with three short cycles of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)/high-fat diet (HF), followed by 2% white tea (w/v), 0.05% epigallocatechin-3-gallate (EGCG), or 0.065% caffeine as sole source of fluid intake. Thirty-two percent of the PhIP/HF controls survived to 1 year, compared with 50%, 48.7%, and 18.2% in groups given white tea, EGCG, and caffeine, respectively. After 1 year, PhIP/HF controls had tumors in the colon, skin, small intestine, Zymbal's gland, salivary gland, and pancreas. For all sites combined, excluding the colon, tumor incidence data were as follows: PhIP/HF 69.5%, PhIP/HF+EGCG 48.7%, PhIP/HF+white tea 46.9%, and PhIP/HF+caffeine 13.3%. Unexpectedly, a higher incidence of colon tumors was detected in rats post-treated with white tea (69%) and caffeine (73%), compared with the 42% incidence in PhIP/HF controls. In the colon tumors, β-catenin mutations were detected at a higher frequency after caffeine post-treatment, and there was a shift towards more tumors harboring substitutions of Gly34, with correspondingly high protein and mRNA expression seen for both β-catenin and c-Myc. c-Myc expression exhibited concordance with tumor promotion, and there was a concomitant increase in cell proliferation versus apoptosis in colonic crypts. A prior report described suppression of PhIP-induced colonic aberrant crypts by the same test agents, but did not incorporate a high-fat diet. These findings are discussed in the context of epidemiological data which do not support an adverse effect of tea and coffee on colon tumor outcome – indeed, some such studies suggest a protective role for caffeinated beverages
Received January 16, 2008; revised February 4, 2008; accepted February 8, 2008.