Intestinal metaplasia -the effect of Acid on the gastric mucosa and gastric carcinogenesis-

Abstract

This review concerns stem cells and their relation to intestinal metaplasia. When gastric regions of mice, Mongolian gerbils or several strains of rats were irradiated with a total dose of 20 Gy of X-rays given in two fractions, intestinal metaplasia was only induced in rats. In addition, it was greatly influenced by rat strain and sex. Alkaline phosphatase (ALP) positive metaplastic foci were increased by administration of ranitidine (H(2) receptor antagonist), crude stomach antigens or subtotal resection of the fundus and decreased by cysteamine (gastric acid secretion stimulator), histamine or removal of the submandibular glands. Recent studies have shown that Cdx2 transgenic mice with gastric achlorhydria develop intestinal metaplasia and that in men and animals, Helicobacterpylori (H. pyrlori) infection can cause intestinal metaplasias that are reversible on eradication. Our results combined with findings for H. pylori infection or eradication and transgenic mice suggest that an elevation in the pH of the gastric juice due to disappearance of parietal cells is one of the principal factors for development of reversible intestinal metaplasia. When different organs were transplanted into the stomach or duodenum, they were found to transdifferentiate into gastric or duodenal mucosae, respectively. Organ-specific stem cells in normal non-liver tissues (heart, kidney, brain and skin) also differentiate into hepatocytes when transplanted into an injured liver. Therefore, stem cells have a multipotential ability, transdifferentiating into different organs when transplanted into different environments. Finally, intestinal metaplasia has been found to possibly increase sensitivity to the induction of tumors by colon carcinogens of the 1,2-dimethylhydrazine (DMH), azoxymethane (AOM) or 2-amino-1-methyl-6-phenylimidazo[4.5-b]pyridine (PhIP) type. This carcinogenic process, however, may be relatively minor compared with the main gastric carcinogenesis process induced by N-methy1-N'-nitro-N-nitrosoguanidine (MMNG) or N-methylnitrosourea (MNU), which is not affected by the presence of intestinal metaplasia. The protocol used in these experiments may provide a new approach to help distinguish between developmental events associated with intestinal metaplasia and gastric tumors.

Keywords: X-irradiation; gastric cancer; glandular stomach; intestinal metaplasia; rat.

Fig. 1

Goblet cells with gastric mucosa (Type A). Alcian blue-PAS staining, ×200. Round and ultramarine stained goblet cells were found in PAS-positive (pink) gastric glands.

Fig. 2

Intestinal crypt without Paneth cells (Type B). Alcian blue-PAS staining, ×200. PAS-negative glands have many goblet cells but no Paneth cells at the bottom.

Fig. 3

Intestinal crypt with Paneth cells (Type C). Alcian blue PAS staining, ×200. Arrows: Paneth cells.

Fig. 4

Gastric mucosa differentiating into an intestinal crypt. Alcian blue-PAS staining, ×200. Arrow: One side is PAS-positive gastric gland and in other hand intestinal type crypt.

Fig. 5

Alkaline phosphatase active stomach.

Fig. 6

Working hypothesis for induction of intestinal metaplasia.

Fig. 7

Flow chart for stem cells in the stomach.