Selenium, copper, and zinc concentrations in intestinal cancer tissue and in colon and rectum polyps.

The prospective randomized trial was used to determine Se, Zn, and Cu concentrations in intestinal cancer tissue and colorectal polyp. We also determined the relationship among the trace element levels in cancer tissue, the localization of neoplasms, and the stage of their development. The concentrations of these trace elements were examined in cancer tissue of the colorectum in 67 patients and in the colon and rectum polyps in 42 patients using the total-reflection X-ray fluorescence (TRXRF) method. The mean concentration of Se in colorectal cancer was 0.86 microg/g tissue and was statistically higher than in the case of polyps (0.57 microg/g). The mean concentration of Zn in colorectal cancer was higher than in the polyp (14.8 microg/g and 9.84 microg/g, respectively). The determined average concentration of Cu in colorectal cancer was 3.87 microg/g tissue and was a little lower than the level of this metal in the polyp (3.94 microg/g). There was no difference in the levels of these trace elements depending on the location of the neoplasm and the stage of its development. Also, there was no difference between the concentrations of these trace elements in the cancer tissue of malignant and benign tumors after taking into consideration the sex and age of patients. During the examination, we determined significantly higher concentrations of only selenium and zinc in the cancer tissue and not in the polyp. The level of copper was lower in a malignant tumor than in a benign one.

Response of Apc(min) and A33 (delta N beta-cat) mutant mice to treatment with tea, sulindac, and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP).

There is growing interest in the potential health benefits of tea, and a recent report described the potent antimutagenic activity of white tea in comparison with green tea against several heterocyclic amines, including 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) [Mutat. Res. 495 (2001) 61]. We compared the inhibitory effects of white and green teas with sulindac, a nonsteroidal anti-inflammatory agent, in two different mouse models of intestinal tumorigenesis. In the Apc(min) mouse, white and green teas given at human-relevant concentrations (1.5% w/v, 2-min brew), and sulindac (80 ppm in the drinking water), each suppressed polyp formation by approximately 50%, and the combination of white tea plus sulindac was more effective than either treatment alone (P=0.05). Mice expressing an N-terminally truncated, oncogenic version of beta-catenin (A 33(delta N beta-cat) mutant mice) developed colonic aberrant crypt foci (ACF) spontaneously, but PhIP treatment increased the incidence and number of ACF per colon. In the normal-looking intestinal mucosa of Apc(min) and A 33(delta N beta-cat) mice, white tea plus sulindac treatment markedly attenuated the expression of beta-catenin protein, and this was recapitulated in vitro in cells transiently transfected with beta-catenin plus Tcf-4 and treated with tea or the major tea polyphenol epigallocatechin-3-gallate (EGCG). Expression of a beta-catenin/Tcf reporter was inhibited by EGCG in the transfected cells, and the beta-catenin/Tcf target genes cyclin D1 and c-jun were downregulated in vivo by tea plus sulindac treatment. Collectively, the data support a chemopreventive role for tea and sulindac against intermediate and late stages of colon cancer, via effects on the beta-catenin/Tcf signaling pathway.