Effects of Antitumor Agents to DNA Synthesis in the Gastric Epithelia of Mice Implanted with Ehrlich Carcinoma Cells: An Autoradiographic Study / 대한해부학회지

This experiment was performed to evaluate the morphological responses of the gastric epithelium of the mouse, inoculated with Ehrlich carcinoma cells, following administration of 5-fluorouracil, adriamycin or mitomycin C. Healthy adult ICR mice weighing 25 gm each were divided into normal control and experimental groups (tumor control group, 5-fluorouracil treated group, adriamycin treated group, and mitomycin C treated group). In the experimental groups, each mouse was inoculated with 1 x 10(7) Ehrlich carcinoma cells subcutaneously in the inguinal area. From next day after inoculations, 0.2 mL of saline, 5-fluorouracil (30 mg/kg), adriamycin (2 mg/kg) or mitomycin C (400 microgram/kg) were injected subcutaneously to the animals every other day, respectively. The day following the 7th injection of anticancer drugs, each mouse was injected with a single dose of 0.7 microCi/gm of methyl-3H-thymidine (25Ci/mmol, Amersham Lab., England) through tail vein. Seventy minutes after the thymidine injection, animals were sacrificed. The number of labeled epithelial cells in the gastric mucosae (mean number of labeled epithelial cells per 3.5 mm length of mucosa) were observed and calculated. On histological study, in the gastric mucosae of adriamycin-treated groups, denatured surface epithelial cells, expanded lumen of the gastric gland, and congested lamina propria were observed. But in the 5-fluorouracil or mitomycin treated groups, severe morphological changes of the gastric mucosae were not observed. On autoradiographic study, numbers of the labeled cells in the gastric mucosae per 3.5 mm length of normal control, tumor control, 5-fluorouracil-treated, adriamycin-treated and mitomycin C treated groups were 267.3 (+/-48.86), 273.6 (+/-59.41), 375.3 (+/-83.36), 15.3 (+/-9.66) and 124.0 (+/-32.66), respectively. In the adriamycin and mitomycin C-treated group, poorly-labeled cells containing only a few silver grains of 3H-thymidine were observed more frequently as compared in those of the normal control group. But in the 5-fluorouracil-treated group, number of the heavy labeled cells were observed more frequently than in those of the normal control group. From the above results, adriamycin and mitomycin C may severely suppress the DNA synthesis of the epithelial cells of the gastric mucosae. But some amount of the 5-fluorouracil (30 mg/kg) may not suppress the DNA synthesis of gastric epithelial cells.

Effects of Helicobacter pylori and non-steroidal anti-inflammatory drugs on proliferation of gastric epithelial cells / 中华消化杂志

Objective To investigate the interactions and effects of Helicobacter pylori (H.pylori) and non steroidal anti inflammatory drugs (NSAID) on the proliferation of gastric epithelial cells in vitro. Methods After co culturing of gastric cancer cell line AGS cells with H.pylori and/or NSAID (indomethacin and aspirin) for 48 hours, the cell proliferation and proliferating cell nuclear antigen (PCNA) were examined by MTT assay and Western blot. Results cagA positive H.pylori strain NCTC11637, but not cagA negative H.pylori strain NCTC12908, had the effect of enhancing gastric epithelium cell proliferation. However, the effect of proliferation was dependent on the density of H.pylori . It was demonstrated that low density (range from 3.2?10 4 CFU/ml to 4?10 6 CFU/ml) of bacteria suspensions resulted in proliferative effect, while high density (more than 2?10 7 CFU/ml) resulted in inhibition. Besides, indomethacin and aspirin inhibited cell proliferation in a dose dependent manner. Moreover, when AGS cells were incubated with cagA positive H.pylori and NSAID, inhibition rather than proliferation was observed. cagA positive H.pylori strains up regulated the expression of PCNA while indomethacin and aspirin down regulated the level of PCNA expression. Meanwhile, the expression of PCNA was also reduced significantly when AGS was co cultured with H.pylori and NSAID. Conclusions The results indicated that gastric epithelium cell proliferation was associated with different H.pylori strains and its density. cagA positive H.pylori strain is prone to increase cell proliferation, but cagA negative H.pylori strain has no such effect. NSAID can inhibit gastric epithelial cell proliferation and reverse such effect caused by H.pylori.

Autoradiographic Study on the Effect of AG60 to the DNA Synthesis of Gastric Epithelium of Mouse Inoculated with Ehrlich Carcinoma / 대한해부학회지

To study the tumor-suppression effect of a newly developed anti-tumor agent AG60 [acriflavine (1) : guanosine (1) composition, Taerim Pharm. Co., Seoul, Korea], each Ehrlich carcinoma (10(7) cells)-inoculated mouse received the subcutaneous injection of 0.2 ml of saline, 5 mg/kg of AG60, and 30 mg/kg of AG60 per day for a week. The day following the last injection, each mouse was injected with a single dose of 0.7 microcurie/g of methyl-3H-thymidine (25Ci/mmol, Amersham Lab., England) through tail vein. Seventy minutes after the thymidine injection, animals were sacrificed, and gastric tissues were collected and fixed in 10% neutral formalin. Tissue blocks were washed, dehydrated, embedded and cut in 6 micrometer-thick sections. Deparaffinized sections were coated with autoradiographic emulsion EM 1 (Amersham Lab. England) in a dark room and dried and were placed in a light-tight box. The sections were exposured for 5 weeks in the dark room, and were then developed in D-19 developer. Labeled indices (mean number of labeled cells per 100 epithelial cells in the isthmus) were observed and calculated. The results are as follows; 1. On histological study, gastric mucosa had no morphological changes following the injection of AG60. 2. On autoradiographic study, labeled grains of 3H-thymidine were restricted on the isthmus portion of the gatric gland. 3. On autoradiographic study, labeling indicies of gastric epithelial cells of normal control, experimental control, AG60 (5 mg/kg)-treated and AG60 (30 mg/kg)-treated groups were 21.9+/-0.28%, 18.8+/-0.03%, 21.6+/-1.61% and 6.3+/-0.93%, respectively. These result suggest that AG60 is expected as one of most effective anticancer drugs, and the dosage under 5 mg/kg of AG60 does not result any defect on the DNA synthesis in gastric epithelial cells.

The mitotic rate of the gastric epithelium of albino rats of various ages.

The stomachs of albino rats of various ages were studied by using routine histological procedures. The mitotic rates of the gastric epithelium of the rats, ranging in age from 1, 5, 9, 13 and 18 to over 24 months were 1.15, 0.20, 0.05, 0.02, 0.02 and 0.01 percent, respectively. The increase of the mitotic rate in growing albino rate was the result of supplying cells for the growth of the stomach. The mitotic rate was constant in the adult specimens while in the older rats, the mitotic rate was obviously decreasing owing to senile changes.