Expression of gastrointestinal glutathione peroxidase and selenoprotein P mRNA in colorectal adenomas

A648 AGA ABSTRACTS G2669 EXPRESSION OF GASTROINTESTINAL GLUTATIIIONE PEROXIDASE AND SELENOPROTEIN P mRNA IN COLORECTAL ADENOMAS. H, Mtirk, M. Scheurlen, C. Beck, S. Karvar, O. Al-Taie, L K6hde, F. Jakob. Medizinische Poliklinik / Klinische Forschergruppe, University of Wiirzburg, Germany Introduction: Selenium, which is discussed as a potential micronutrient in the prevention of colorectal cancer, is an essential component of Selenoprotein P (SeP) and the gastrointestinal glutathione peroxidase (GI-GPX). Glutathione peroxidases reduce lipidic and nonlipidic hydroperoxides, using reduced glutathione as cosubstrate. The gastrointestinal isoenzyme GI-GPX plays an important role in the antioxidant defense of the human digestive tract. SeP, a heavily glycosylated, secreted protein of still unknown function, is suggested to be involved in redox-regulation. Therefore, we studied the expression of SeP and GI-GPX mRNA in colorectal adenomas as well as in the normal surrounding mucosa. Methods: Biopsies were obtained from colorectal adenomas and the macroscopically and histologically normal adjacent mucosa. Total RNA was extracted from the tissue samples, and the expression of SeP and GI-GPX was determined by Northern blot analysis. As a reference, pooled tissue samples from macroscopically and histologically normal mucosa were obtained. Results: Abundant mRNA signals of GI-GPX and SeP in the normal colon mucosa were previously described by our group. In the biopsy samples obtained from adenomas, GI-GPX mRNA levels were increased, whereas only weak signals were detected in the surrounding mucosa. In contrast, SeP mRNA expression in the adenoma specimens was markedly reduced, as compared to high levels in normal adjacent tissue. Discussion: According to animal models and epidemiological data, low selenium levels may facilitate the development of colorectal cancer. As a potential mechanism, selenocysteine-containing proteins could be involved in tumor inhibition by protection against oxidative injury. The markedly increased expression of GI-GPX found in our study may support this hypothesis. Because of the still unknown biological function of SeP, the very low expression of SeP mRNA in adenomas is difficult to explain. The downregulated gene expression of SeP in colorectal adenomas as compared to the adjacent mucosa indicates a connection with different stages of cell differentiation and proliferation.

GASTROENTEROLOGY Vol. 114, No. 4 major source of nitrite to the upper GI tract. We have investigated the effect of a nitrate meal on intragastric concentrations of nitrite and ascorbic acid. Subjects and Methods: Twenty healthy volunteers were studied, mean age 30 years (range 20 to 47). Fasting samples of saliva, gastric juice and serum were obtained. A solution of potassium nitrate (nitrate content equivalent to a salad meal) was infused via a nasogastric tube and further samples taken over 2 hours for analysis of nitrate, nitrite, ascorbic acid and total Vitamin C (TVC). Results: Following the nitrate meal, there was a rise in serum nitrate and saliva nitrite (which peaked at 40 mins) and this was accompanied by a profound fall in gastric juice ascorbic acid (AA). fasting

40 mins post meal 120 mins post meal

Intragastric pH 1.6 (1-7.4) 1.3 (1-2.6) 1.5 (1.1-3.2) serum nitrate 24 (12-67) 82 (49-131) 56 (20-107) salivary nitrite 44 (0-306) 262 (5-939) 220 (3-1122) gastric nitrite 0 (0-12) 0 (0-156) 3 (0-179) gastric AA 3.8 (0.3-20.7) 1.3 (0.3-26.6) 2.3 (0.4-25.9) gastric TVC 5.0 (1.2-21) 5.1 (1.7-28.3) 6.0 (1.7-33.2) AA/TVC ratio 0,76 (0.25-1.0) 0.35 (0.1-0.94) 0.44 (0.09-0.83) Units: nitrate, nitrite ~mol/1). AA, TVC ~ug/ml). Values are medians (range). There was a strong correlation between the rise in saliva nitrite and the fall in the gastric AA/TVC ratio (r=-0.52, p