Effects of 5-Fluorouracil, Mitomycin C or AG60 to the DNA Synthesis of Rectal Epithelium of Mice Implanted with Ehrlich Carcinoma Cells

Ko, Jeong Sik; Ahn, E Tay; Park, Kyung Ho; Park, Dae Kyoon; Jung, Eun Joo

Abstract

This experiment was performed to evaluate the morphological responses of the intestinal gland of the mouse, rectum inoculated with Ehrlich carcinoma cells, following administration of 5- fluorouracil, mitomycin C or AG60. Healthy adult ICR mice weighing 25 gm each were divided into normal and experimental groups (tumor control group, 5-fluorouracil, mitomycin C treated group, and AG60 treated group). In the experimental groups, each mouse was inoculated with 1*10 (7) Ehrlich carcinoma cells subcutaneously in the inguinal area. From next day, 0.2 mL of saline, 5-fluorouracil (30 mg/kg), mitomycin C (400 microgram/kg) or AG60 (5 mg/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 through tail vein. Seventy minutes after the thymidine injection, animals were sacrificed. The number of the labeled epithelial cells of the rectal crypts (mean number of labeled epithelial cells per 3.5 mm length of mucosa) were observed and calculated. On histological study, in the rectum of mitomycin C treated groups, narrowed intestinal gland, a number of the nectotic changed epithelial nuclei and loosely arranged lamina propria were observed. But in the AG60 treated group, morphological changes of the rectum were not observed. On autoradiographic study, number of the labeled cells of normal control, tumor control, 5-fluorouracil (30 mg/kg) treated, mitomycin C (400 microgram/kg) treated and AG60 (5 mg/kg) treated groups were 246.3+/-42.30, 253.8+/-20.54, 172.7+/-19.02, 108.7+/-17.67 and 53.8+/-11.70, respectively. In the AG60 and mitomycin C treated group, poorly-labeled cells containing only a few silver grains of 3H-thymidine were observed more frequently than in those of the normal control group. From the above results, AG60 (5 mg/kg) and mitomycin C (400 microgram/kg) are more suppressed the DNA synthesis of the cells of the rectal crypts as compare with 5- fluorouracil (30 mg/kg). And AG60 does not result any histological defect on the rectal mucosa. These results suggest that AG60 is expected as one of most effective anticancer drugs.