Effects of Antitumor Agents to the DNA Synthesis of Cecal Mucosa of Mouse

Na, Ji Ung; Ahn, E Tay; Park, Kyung Ho; Park, Dae Kyoon; Ko, Jeong Sik

Abstract

This experiment was performed to evaluate the morphological responses of the cecal mucosa of the mouse, inoculated with Ehrlich carcinoma cells in the inguinal area, following administration of 5-fluorouracil, mitomycin C or adriamycin. Healthy adult ICR mice weighing 25 gm each were divided into normal and experimental groups. In the experimental groups, each mouse was inoculated with 1 x 10(7) Ehrlich carcinoma cells subcutaneous in the inguinal area. From next day, 0.2 mL of saline, 5-fluorouracil (30 mg/kg), mitomycin C (400 microgram/kg) or adriamycin (2 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 micro Ci/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 the labeled epithelial cells of the cecal crypts (mean number of labeled epithelial cells per 3.5 mm length of mucosa) were observed and evaluated. On histological study, in the experimental control and mitomycin C-treated mice, general morphology of the cecal mucosae was similar. And in the 5-fluorouracil-treated mice, slightly swelled epithelial cells and expanded lumen of the intestinal crypts were observed. But in the adriamycin-treated groups, slightly disrupted intestinal crypts, a large number of basophilic epithelial cells and the expanded lumen of the intestinal crypts were observed. On autoradiographic study, number of the labeled cells of normal control, experimental control, 5-fluorouracil treated, mitomycin C-treated, or adriamycin-treated groups were 362.2+/-56.12, 350.7+/-71.13, 215.7+/-80.55, 144.2+/-34.60 and 125.0+/-37.45, respectively. In the adriamycin and mitomycin C-treated groups, poorly-labeled cells containing only a few silver grains were observed more frequently than in those of the normal and experimental control groups. From the above results, adriamycin and mitomycin C suppressed the DNA synthesis of the epithelial cells of the cecal mucosa more severely as compared with 5-fluorouracil did. Especially, adriamycin was more harmful than mitomycin C and 5-fluorouracil on the cecal mucosae.