Protective versus promotional effects of white tea and caffeine on PhIP-induced tumorigenesis and beta-catenin expression in the rat.
A 1 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 (HF) diet, followed by 2% white tea (wt/vol), 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, beta-catenin mutations were detected at a higher frequency after caffeine posttreatment, and there was a shift toward more tumors harboring substitutions of Gly34 with correspondingly high protein and messenger RNA expression seen for both beta-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 HF 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.
Wang
Rong
R
Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA.
Dashwood
W Mohaiza
WM
Löhr
Christiane V
CV
Fischer
Kay A
KA
Pereira
Clifford B
CB
Louderback
Mandy
M
Nakagama
Hitoshi
H
Bailey
George S
GS
Williams
David E
DE
Dashwood
Roderick H
RH
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D002110:Caffeine / Q000633:toxicity*; D002273:Carcinogens; D002392:Catechin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000517:prevention & control; D007093:Imidazoles; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D051381:Rats; D016019:Survival Analysis; D013662:Tea; D051176:beta Catenin / Q000235:genetics*
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D007093:Imidazoles; D013662:Tea; D051176:beta Catenin; D002110:Caffeine; D002392:Catechin; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; C045651:epigallocatechin gallate