Generative Cell Zone Research Articles

Morphological changes of gastric mucosa depending on functional dyspepsia syndrome.

Background. Chronic gastritis process of cell renewal in the mucosa is disturbed, leading to rapid movement of the generative cell zone without full differentiation into mature specialized area accommodation epithelial cells. The result of this process is the inability to fully function gastric glands. Crucial in the diagnosis of gastritis given the nature of the morphological changes of the gastric mucosa and preferential localization of these changes. Objective. To assess histological changes of gastric mucosa in patients with clinically different types of functional dyspepsia. Methods. Adult patients (18-65 years) with confirmed diagnosis of functional dyspepsia were eligible to participate. Biopsy specimens were taken from stomach due to the Houston-updated gastric biopsy sampling protocol for the next histological examination. One expert gastrointestinal pathologist assessed all tissue samples. Atrophy was assessed due to Operative Link for Gastritis Assessment (OLGA) staging system. Results. 75 patients were recruited, 42 of which had epigastric pain (I group) and 33 – postprandial distress syndrome (II group) due to Rome III criteria (2006). Antral and corpus atrophy were detected at the same frequency in both groups (p>0.05), however the stage of atrophy didn’t exceed I in all cases. Complete antral metaplasia was revealed in 11 (26.2%) patients of the I group and 11 (33.3%) patients of the II one. Incomplete antral metaplasia was seen in 2 (4.7%) patients of the I group and 2 (6.1%) patients of the II one. No cases of corpus metaplasia or dysplasia were found. Conclusion. Our study didn’t reveal statistically significant correlation between stage of gastritis, atrophic or metaplastic changes and clinical symptoms of functional dyspepsia.

A monoclonal antibody, PGM34, against 6‐sulfated blood‐group H type 2 antigen, on the carbohydrate moiety of mucin

Mucin, a major component of mucus, is a highly O-glycosylated, high-molecular-mass glycoprotein extensively involved in the physiology of gastrointestinal mucosa. To detect and characterize mucins derived from site-specific mucous cells, we developed a monoclonal antibody, designated PGM34, by immunizing a mouse with purified pig gastric mucin. The reactivity of PGM34 with mucin was inhibited by periodate treatment of the mucin, but not by trypsin digestion. This suggests that PGM34 recognizes the carbohydrate portion of mucin. To determine the epitope, oligosaccharide-alditols obtained from pig gastric mucin were fractionated by successive gel-filtration, ion-exchange, and normal-phase HPLC, and tested for reactivity with PGM34. Two purified oligosaccharide-alditols that reacted with PGM34 were obtained. Their structures were determined by NMR spectroscopy as Fucalpha1-2Galbeta1-4GlcNAc(6SO(3)H)beta1-6(Fucalpha1-2Galbeta1-3)GalNAc-ol and Fucalpha1-2Galbeta1-4GlcNAc(6SO(3)H)beta1-6(Galbeta1-3)GalNAc-ol. None of the defucosylated or desulfated forms of these oligosaccharides reacted with PGM34. Thus, the epitope of PGM34 was determined as the Fucalpha1-2Galbeta1-4GlcNAc(6SO(3)H)beta- sequence. Immunohistochemical examination of rat gastrointestinal tract showed that PGM34 stained surface mucous cells close to the generative cell zone in the gastric fundus and goblet cells in the small intestine, but only slightly stained antral mucous cells in the stomach. These data, taken together, show that PGM34 is a very useful tool for elucidating the role of mucins with characteristic sulfated oligosaccharides.

Apoptosis in gastric epithelium induced by Helicobacter pylori infection: implications in gastric carcinogenesis.

Helicobacter pylori is an identified carcinogen for gastric cancer, however, the underlying mechanisms remain to be defined. In this review, we sought to elucidate the role of apoptosis in gastric carcinogenesis, to determine the influence of H. pylori infection on apoptosis, and finally to provide insights into the mechanisms by which H. pylori may lead to gastric carcinogenesis. A broad-based MEDLINE and Current Contents literature search was performed to identify relevant publications between 1966 and March 2000 addressing H. pylori infection, apoptosis, cell proliferation, gastric carcinoma, oncogenes, and tumor suppressor genes, as well as the products of these genes. Abstracts from recent major conferences that provided adequate additional data were also included. Apoptotic cells are rare in the glandular neck region (the generative cell zone) of normal gastric mucosa. With progression of atrophic gastritis, the generative cell zone shifts downward and a relatively large number of apoptotic cells occur. In intestinalized glands, both apoptotic cells and proliferative cells are present in deeper portions of the glands, corresponding to the generative zone. A higher frequency of apoptosis has been observed in gastric dysplasia than in coexisting gastric carcinomas, whereas the number of proliferative cells is significantly higher in gastric carcinoma than in dysplasia. Upregulation of oncogene bcl-2 in premalignant lesions and "downregulation" of the gene after malignant change is probably a common event. Accumulation of p53 protein is first detected in dysplasia, although mutation of the pS3 gene may occur in intestinal metaplasia. H. pylori infection induces apoptosis in gastric epithelial cells, which returns to normal after eradication of the infection. Numerous molecules produced by H. pylori including cytotoxin (VacA), lipopolysaccharide, monochloramine, and nitric oxide may directly induce apoptosis. Moreover, H. pylori-stimulated host inflammatory/immune responses lead to release of a large amount of cytokines. Cytokines produced by type 1 T helper cells, such as TNF-alpha and IFN-gamma, markedly potentiate apoptosis. Gastric cell proliferation is significantly higher in patients with H. pylori infection than in normal controls, and eradication of the infection leads to a reduction in cell proliferation. Apoptosis and cell proliferation are also increased in precancerous lesions such as gastric atrophy, intestinal metaplasia, and dysplasia in the presence of H. pylori infection. However, H. pylori-induced apoptosis may no longer be cell cycle-dependent in these lesions because of the occurrence of alterations and mutations of apoptosis-regulating genes, resulting in a loss of balance between apoptosis and cell proliferation. It is hypothesized that H. pylori-induced apoptosis may play a key role in gastric carcinogenesis by increasing cell proliferation and/or resulting in gastric atrophy.

Pathological Features of Helicobacter pylori-Induced Gastritis in Mongolian Gerbils.

Seven-week-old male specific pathogen-free Mongolian gerbils (MGS/Sea) were orally inoculated with 2 × 108 colony-forming units per animal of a broth culture of Helicobacter pylori (H. pylori) ATCC 43504. Histopathological examination of their stomachs after 6 weeks of post inoculation revealed gastritis with hemorrhage, inflammatory cell infiltration, superficial erosion, mucosal thickening, and lymph follicles, in the pyloric mucosa and the fundic mucosa near the transitional zone. In addition, loss of fundic glands and appearance of hyperplastic epithelium with pseudopyloric glands containing paradoxical concanavalin A reactive mucins were evident in the fundic mucosa near the transitional zone. H. pylori bacteria were detected in the surface mucous gel layer lining inflamed mucosa or in the foveolar pits of the same regions. Galactose oxidase-cold thionine Schiff reactive mucins in the surface mucous cells were decreased. BrdU-labeled mucosal epithelial cells were markedly increased, and the generative cell zone was expanded. These features resemble human gastritis associated with H. pylori.

Regulation of apoptotic cell death in the pyloric glands of the canine stomach.

In gastrointestinal epithelia, apoptosis has been thought to play a part in the shedding of postmitotic cells into the lumen. However, we have found that apoptosis more frequently in the generative cell (G) zone (the lower one third of the pit) than in the luminal zone (the upper one third of the pit) and the gland zone in the canine pyloric gland. To analyse the regulation of apoptotic cell death in each zone, we labelled S-phase cells by single and repeated injections of bromodeoxyuridine (BrdU) i.v. at intervals of 8 h. We found that 30% of apoptoses in the G zone were flash-labelled by BrdU and might derive from cells in or just after the S phase. The incidence of apoptosis and mitotic index did not change significantly after repeated injections of BrdU until the 49-h point, when the incidence of apoptosis increased and the mitotic index decreased significantly in the G zone, while the incidence of apoptosis decreased in the luminal zone. The BrdU-induced increase of apoptosis and cell-cycle arrest at the 49-h point may be caused by enhanced DNA mispairs that are elicited by incorporation of BrdU, in particular using the template of BrdU incorporated DNA. Apoptosis in the luminal zone may be down-regulated by reduced cell production in the G-zone.

Apoptosis in human gastric mucosa, chronic gastritis, dysplasia and carcinoma: analysis by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling.

We examined the existence and distribution of apoptotic cells in human gastric mucosa, chronic gastritis, adenomatous dysplasias and carcinomas in 15 surgically removed stomachs in which dysplasia and carcinoma were found simultaneously. Serial sections were cut for immunohistochemistry for p53 oncoprotein and Ki-67 antigen, and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labelling (TUNEL). TUNEL signal-positive apoptotic cells were rare in normal mucosa, while a few apoptotic cells were noted in gastritic mucosa and intestinal metaplasia, intermingled with Ki-67 antigen-positive cells forming a generative cell zone. This suggests the cell-cycle-dependent apoptosis of gastric mucosa. The frequency of apoptotic cells per crypt was higher in incomplete than in complete metaplasia, implying greater underlying DNA damage in the former. TUNEL indices (TI: percentage of TUNEL-positive cells in tumour cells) were slightly higher in adenomatous dysplasias (4.9 +/- 2.1) than in carcinoma (3.9 +/- 1.1), but there was no no statistical difference. Ki-67 indices (KI: percentage of Ki-67 antigen-positive cells in tumour cells) were significantly (P < 0.05) higher in carcinomas than in dysplasias. Thus, gastric adenomatous dysplasias were characterized by relatively higher TI and lower KI, which might reflect a more static growth potential. The expression of p53 oncoprotein in cancer cells is thought to be an apoptosis-suppressing event, although its precise role remains to be elucidated. Overall, these results indicate that apoptosis plays a crucial part in the morphogenesis of gastritic mucosa including intestinal metaplasia, and that the process is correlated both with tumourigenesis and with proliferative activity.

Detection of Cholecystokinin B/Gastrin Receptor mRNA Expressing Cells in the Stomach of Hypergastrinemic Rats.

Enterochromaffin-like (ECL) cells, which are numerous in the oxyntic mucosa of the rat stomach, proliferate in the presence of hypergastrinemia. We investigated the distribution of cells expressing gastrin receptor (GR) in Sprague-Dawley rats in which hypergastrinemia was induced by partial gastric corpectomy. The ECL cell density was determined by immunohistochemical staining for histamine. The expression of GR mRNA was investigated using digoxigenin-labeled complementary RNA probes. The labeling index of the generative cell zone was determined by 3H-thymidine autoradiography. The ECL cell density and the labeling index in the generative cell zone increased in association with increased plasma levels of gastrin after 24 weeks (p<0.05). The expression of GR mRNA was seen not only in ECL, generative, parietal and chief cells, but also in stromal cells of hypergastrinemic rats. The expression of GR mRNA became more marked in the oxyntic mucosa as plasma levels of gastrin increased, and it was suggested that GR mRNA expression acts as one indication in the development of ECL cell hyperplasia.

Histogenesis of hyperplastic polyps of the stomach in terms of cellular proliferation

We investigated the histogenesis of hyperplastic polyps of the stomach, in terms of cellular proliferation, by studying endoscopically removed and gastrectomized human gastric polyps either labeled with bromodeoxyuridine (BrdU) by in vitro flash labeling techniques or labeled in an isolated organ circulation system, in both of which, perfluorochemical artificial blood was employed. Immunohistochemistry with antibodies against BrdU and proliferating cell nuclear antigen (PCNA) was simultaneously employed. The generative cell zone of pedunculated and semipedunculated polyps was markedly expanded compared with that of the background mucosa, and this change also appeared in sessile polyps, although to a lesser degree. Enhanced proliferative activity was observed in both epithelial and stromal cells in areas of erosion. Our results demonstrate that the initial change in the histogenesis of hyperplastic polyps is an expansion of the generative cell zone, followed by interstitial edema and stromal cell proliferation, and that erosion can facilitate these changes. No correlation was found between the size of the polyps and the labeling indices. This finding explains, in part, the diversity of chronological changes in the size and shape of hyperplastic polyps.

The effect of sofalcone on the kinetics of the generative cells and superficial epithelial cells in mouse gastric mucosa

Effects of an anti-ulcer drug, 2'-carboxymethoxy-4,4'-bis(3-methyl-2-butenyloxy) chalcone (sofalcone), on the generative cells and kinetics of superficial epithelial cells in mouse gastric mucosa, including the effect of hydrocortisone on them, were investigated by the use of 3H-thymidine autoradiography. The labeling indices and the width of the generative cell zone in the fundic mucosa were significantly decreased by administration of hydrocortisone. The decrease in the labeling indices and the width of the generative cell zone induced by administration of hydrocortisone were not inhibited by sofalcone. Hydrocortisone had no significant influence on the labeling indices of the generative cell zone in the pyloric mucosa, but decreased the width of it. The decrease in the width of the generative cell zone induced by hydrocortisone was inhibited by sofalcone. Concerning the influence on the kinetics of superficial epithelial cells, hydrocortisone inhibited the increase in the labeling indices of the superficial epithelial cells after continuous administration of 3H-thymidine in both the fundic mucosa and pyloric mucosa. In the fundic mucosa, sofalcone showed no influence on the inhibition by hydrocortisone, but in the pyloric mucosa, the effect of hydrocortisone was abolished by sofalcone. These results suggest that sofalcone inhibits the reduction of the cell production and the prolongation of the life span of superficial epithelial cells caused by hydrocortisone in the pyloric mucosa.

Effect of Sofalcone on the Gastric Cell Proliferation in the Experimental Gastritis of Rats

Effects of sofalcone on the morphometrical glandular structure and the generative cell proliferation in the gastric mucosa of gastritis, induced in rats by the treatment of sodium taurocholate (TCA) for 3 and 6 months, were examined by means of 3H-thymidine autoradiography. Morphometrical observation revealed that the ratios of the length of the glandular portion/the total length of the gastric gland were generally decreased in both fundic and pyloric glands with TCA treatments, which may indicate mucosal atrophy. These atrophic changes were improved to the normal levels by the administration of sofalcone for 3 weeks after the treatment of TCA. On the other hand, cell proliferative activity, indicated by the labeling indexes in the generative cell zone of gastric mucosa, was increased in TCA induced gastritis rat, which seems to be the response to replace the increased cell loss. The administration of sofalcone to the gastritis rats further increased the labeling indexes, especially in pyloric gland with statistical significance in both TCA treated rats for 3 and 6 months. From these results, it is suggested that sofalcone stimulates the compensatory increase of proliferative activity of generative cells, which would be available to repair the-gastric mucosa with gastritis.

Effect of sofalcone on the gastric cell proliferation in the experimental gastritis of rats.

Effects of sofalcone on the morphometrical glandular structure and the generative cell proliferation in the gastric mucosa of gastritis, induced in rats by the treatment of sodium taurocholate (TCA) for 3 and 6 months, were examined by means of 3H-thymidine autoradiography. Morphometrical observation revealed that the ratios of the length of the glandular portion/the total length of the gastric gland were generally decreased in both fundic and pyloric glands with TCA treatments, which may indicate mucosal atrophy. These atrophic changes were improved to the normal levels by the administration of sofalcone for 3 weeks after the treatment of TCA. On the other hand, cell proliferative activity, indicated by the labeling indexes in the generative cell zone of gastric mucosa, was increased in TCA induced gastritis rat, which seems to be the response to replace the increased cell loss. The administration of sofalcone to the gastritis rats further increased the labeling indexes, especially in pyloric gland with statistical significance in both TCA treated rats for 3 and 6 months. From these results, it is suggested that sofalcone stimulates the compensatory increase of proliferative activity of generative cells, which would be available to repair the gastric mucosa with gastritis.

Effect of Sofalcone on the Gastric Cell Proliferation in the Experimental Gastritis of Rats

Effects of sofalcone on the morphometrical glandular structure and the generative cell proliferation in the gastric mucosa of gastritis, induced in rats by the treatment of sodium taurocholate (TCA) for 3 and 6 months, were examined by means of 3H-thymidine autoradiography. Morphometrical observation revealed that the ratios of the length of the glandular portion/the total length of the gastric gland were generally decreased in both fundic and pyloric glands with TCA treatments, which may indicate mucosal atrophy. These atrophic changes were improved to the normal levels by the administration of sofalcone for 3 weeks after the treatment of TCA. On the other hand, cell proliferative activity, indicated by the labeling indexes in the generative cell zone of gastric mucosa, was increased in TCA induced gastritis rat, which seems to be the response to replace the increased cell loss. The administration of sofalcone to the gastritis rats further increased the labeling indexes, especially in pyloric gland with statistical significance in both TCA treated rats for 3 and 6 months. From these results, it is suggested that sofalcone stimulates the compensatory increase of proliferative activity of generative cells, which would be available to repair the-gastric mucosa with gastritis.

The histogenesis and early invasion of gastric cancer.

A three-dimensional analysis of the histogenesis of gastric cancer was made by examining minute, microscopic lesions of less than 500 mu. Cancer develops from the generative cell zone (G-zone) of the atrophic gastric glands and intestinal metaplastic glands. They then bud or branch and infiltrate into the propria interstitial tissue. The G-zone of the cancerous glands showed marked expansion with complete loss of normal cell kinetics of gastric glands and with hardly any signs of differentiation into pyloric glands. In the adjacent glands there were also expansion of the G-zone and formation of loop-shaped glands with abnormal branching and anastomosis sometimes leading to the formation of a network of glands. These changes are compatible with those of abnormal differentiation accompanying atrophy or intestinal metaplasia and are considered to express a preinvasive cancer.

Immune aspects of intestinal metaplasia of the stomach: an immunohistochemical study.

Immune characteristics of intestinal metaplasia of the stomach were analyzed by the immunoperoxidase technique in frozen and paraffin-embedded specimens. In fetal and minimally inflamed adult gastric mucosa, secretory component (SC) was absent from epithelial cells. Non-intestinalized gastric mucosa with evident inflammatory changes showed weak SC immunoreactivity at the generative cell zone. Enhanced immunoreactivity of SC with evidence of transepithelial transport of IgA and IgM, but not of IgG, was demonstrated in intestinalized glands of either the complete or incomplete type. The number of inflammatory cells and lymphoid follicles was decreased in intestinalized mucosa when compared with that in non-intestinalized gastritic mucosa; J chain-negative IgG plasma cells and T cells, both of which were fairly abundant in the latter mucosa, were remarkably decreased in the former mucosa, whereas the decrease of J chain-positive IgA or IgM plasma cells was slight or equivocal. In either mucosa, IgA was the most popular immunoglobulin class in plasma cells. IgD plasma cells were very rare. In the germinal centers of lymphoid follicles which were preferentially distributed in non-intestinalized gastritic mucosa, IgM or IgG germinocytes predominated over IgA germinocytes, and a few T cells and NK cells also were present. Intraepithelial lymphoid cells with a T-suppressor phenotype were detected in intestinalized glands. The possibility that intestinal metaplasia is an adaptation to long-standing chronic gastritis is discussed.

Cells of origin in human gastric neoplasms

The epithelium of the surface mucosa of the human stomach is demonstrated to share an antigen (HP-DU-1) with human pancreatic ductal cell surface epithelium detectable by a murine monoclonal IgG. This marker was found to be characteristic of the epithelium of gastric surface mucosa and serves to distinguish these cells from the epithelium of gastric glands, the generative cell zone, the parietal and mucous neck cells. The absence of HP-DU-1 was confirmed in the epithelium of the small and large intestines, gall bladder, tracheobronchial trees, urinary bladder, intrahepatic bile ducts, prostatic and salivary glands. This surface marker was used to examine the participation of the surface mucosal cell in hyperplastic, preneoplastic and neoplastic lesions of the human gastric mucosa. Gastric hyperplastic polyps and polypoid hypertrophic gastritis were mainly composed of epithelium bearing HP-DU-1 antigens. In contrast epithelial cells of atrophic gastritis, atrophic gastritis with intestinal metaplasia, and adenocarcinoma of the stomach lacked this antigen.

Studies on Histogenesis of the Gastric Carcinoma Using Minute Cancers

Summary Histopathologically, we examined 53 lesions, in 13 cases, of minute cancers measuring less than 5 mm in the largest diameter, in order to study the histogenesis of gastric cancer. Forty-four lesions in four cases were undifferentiated adenocarcinoma, and nine lesions in nine cases were differentiated adenocarcinoma. Cancer cells of the undifferentiated type were confined to the lamina propria of the mucosa, especially near the generative cell zone of the neck of the gastric pit, and had a tendency to extend to the surface as the size of the minute cancer increased. The surrounding mucosa was ordinary epithelia of the stomach without intestinal metaplasia. Atrophy of the pseudopyloric and fundic glands was seen at the lesions with inflammatory-cell infiltration. Cancer cells of the differentiated type had a tendency to involve the entire thickness of the mucosa by replacing the epithelia of the gastric pits. The surrounding mucosa was composed of markedly intestinalized epithelia. And the border between the cancer cell and the intestinalized epithelial cell was sharp. Atrophy of the pseudopyloric and pyloric glands was seen at the lesions with inflammatory-cell infiltration. We conclude that both types of carcinomas occur from the generative cell zone of the gastric pit. Cancer cells of the undifferentiated type may originate in the ordinary mucosa of the stomach, penetrate the basement membrane of the epithelia of the gastric pit and appear in the lamina propria. On the other hand, cancer cells of the differentiated type seem to originate in the intestinalized epithelium and extend to replace the epithelia of the gastric pits.

Tritiated Thymidine Autoradiographic Study on Histogenesis and Spreading of Intestinal Metaplasia in Human Stomach

The non-diseased portions of the antral mucosa of patients suffering from gastric cancer or ulcer were biopsied. The biopsy specimens were then labelled with 3H-thymidine in vitro, and distribution of the labelled epithelial cells in the normal pyloric and in the intestinalized mucosa was studied with autoradiography, and modes of histogenesis and spreading of the intestinal metaplasia were studied, and kinetic characteristics of the intestinalized mucosa were discussed. In the normal pyloric mucosa, the labelled cells were confined to the isthmus region (the middle one-third level of the mucosa), indicating that the surface epithelial and the pyloric glandular cells are normally replaced from the isthmus region. On the other hand, a zone of the labelled cells was found at the lower one-third level in the intestinalized mucosa. The absorptive and the goblet cells in the intestinalized mucosa appear to be renewed by about 70 hours in a fashion similar to that of the small intestine. Microscopic and autoradiographic analysis of the antral mucosa in the course of intestinalization indicates that the intestinal metaplasia begins in the isthmus region of the pyloric glandular tubules of an intact mucosa unaffected by gross injury through transformation of the generative cells from a pyloric to an intestinal pattern. This permits the pyloric lining cells to be replaced with intestinal villous cells and also permits the generative cell zone of the intestinal tubules to shift from the isthmus to the base of the gland until the process is complete. The downward shift of the intestinal tubules occurs in a framework of one of the branched pyloric glands and other glands disappear, resulting in a change of mucosal architectures of the antrum from a branched to a simple tubular gland. The intestinal metaplasia spreads in the mucosa through multi-focal (and sporadical) transformation of the neck generative cells in individual glandular tubules.

On cell proliferation and differentiation of the fundic mucosa of the golden hamster

A fractographic study combined with light and transmission electron microscopy and3H-thymidine autoradiography was carried out to examine cell proliferation and differentiation of the fundic mucosa. The following results were obtained. 1. A gastric gland and a gastric pit into which the gland opens constitute an inseparable structural unit. This unit is called glandular tubule. The glandular tubule consists of an upper, smooth tubular portion and a lower, knobby gastric gland. The tubular portion corresponds to the gastric pit viewed from outside. The so-called isthmus of the gland in which generative cells are confined corresponds to the part of the tubular portion immediately above the constriction. 2. Each glandular tubule of the mucosa is supported by connective tissue only around the tubular portion. The generative cell zone in it appears to be tightly enclosed in a stromal sheath. 3. Surface epithelial cells as well as parietal, mucous neck and chief cells lie outside the stromal sheath and these cell types do not incorporate 3H-thymidine. Mucous neck cells that lie between parietal cells in the upper part of the gastric gland are morphologically similar to the undifferentiated cells of the constriction. 4. From these results, it is suggested that undifferentiated proliferative cells confined to the stromal sheath, when free of the latter, grow and mature as they migrate. The parietal cell arises directly from the undifferentiated cell at the constriction, and it is suggested that the mucous neck cell is an immature form of the chief cell migrating from the generative cell zone.

Dynamic analysis of the stomach epithelium - 3H-thymidine autoradiographic study

The cellular proliferation and differentiation of the stomach epithelium of the hamster were studied by the 3H-thymidine autoradiography. In comparison, autoradiographs of human materials, such as gastric cancer were analysed using “local labeling” of 3H-thymidine.The results obtained are as follows:1. The generative cell zone at the junction between the surface and the glandular epithelium of the hamster stomach was demonstrated by the 3H-thymidine autoradiography.The generative cells possess basophilic cytoplasm and ovoid large nuclei. The mitotic figures are frequent among these cells. Relative size of the nuclei of the generative cell is distributed between unity and two, reflecting their constant DNA sythesis and division. The generative cells are detected in the cardiac gland, the fundic gland and the pyloric gland. Some generative cells show positive PAS reaction. Two hours after injection of 3H-thymidine, labeling indices of the generative cells are 30, 25 and 30 percent in cardiac gland, in fundic gland and in pyloric gland, respectively.The labeling index of the PAS positive generative cells is lower than that of the other generative cells.2. By pursuit of the labeled cells with lapse of time, it is proved that the generative cells differentiate to the surface epithelium and the glandular cells.3. Chasing migration of the labeled cells the life span of the surface epithelium are estimated as 48 hours, 3 days and 3 days in cardiac, fundic and pyloric gland, respectively.4. By the cumulative labeling of 3H-thymidine the life span of the glandular cells were 3 days in cardiac gland. In fundic gland it is more than 21 days and in pyloric gland 7-10 days.5. The generation time of the generative cells are calculated about 25 hours in cardiac gland, 30 hours in fundic gland and 25 hours in pyloric gland.6. The surface epithelium, the generative cells and the glaudular cells in each portion of the stomach constitute respective cell compartment keeping constancy in cell numbers.7. The generative cell compartment plays an important role as source of differentiated cells. The bulk of the each cell compartment is kept constant on the balance which depends on both the generation time of the generative cells and the life span of the maturative cells. The maturative cells consist of the surface epithelium and the glandular cells.The tissue structure of the normal stomach epithelium perpetuates in spite of the constant renewal of the constituent cells. This is assured through the mechanism controlling the generation time of the generative cells and the life span of the maturative cells.8. By 3H-thymidine autoradiography after Polymixin B injection, labeling index of the generative cells increases distinctly than normal. The labeling index was 40-50 percent. Incorporation of 3H-thymidine is found in some parietal cells in fundic gland after the Polymixin B injection, but not in the surface epithelium and the other glandular cells.9. The local labeling technique of 3H-thymidine autoradiography is applied to human stomach epithelium by at time of the surgical operation. These materials include gastric ulcers and gastric cancers. The generative cell zone is found in the transitional portion between the surface epithelium and the glandular cells of the fundic gland and pyloric gland. The labeling index was about thirty percent.10. The generative cell compartment of the pyloric gland of the human stomach varies in size at different places. The glandular cells are absent in some portion of the pyloric gland replaced by the generative cells.11. The eroded lesion of the surface epithelium is later covered by the proliferating generative cells without the cellular differentiation. Therefore the generative cell zone was extended than in the normal state.