5-Fluorouracil 및 Mitomycin C가 Ehrlich 암세포를 이식한 생쥐 위점막 으뜸세포의 미세구조에 미치는 영향 = Ultrastructural Alterations in the Gastric Chief Cells of Mouse, induced by 5-Fluorouracil or Mitomycin C

국문 초록 (Abstract)

이 연구는 생쥐의 샅부위에 Ehrlich 암세포를 이식한 후 5-fluorouracil 또는 mitomycin C를 투여하였을 때, 위점막 으뜸세포 (chief cell)의 미세구조에 미치는 영향을 알기 위하여 시행하였다. 실험동물로는 체중 25g 내외의 ICR생쥐를 사용하였으며 정상대조군과 실험군으로 구분하였다. 정상대조군 이외의 실험군 동물들은 샅부위 피부밑조직에 Ehrlich암세포를 이식한 후, 다음날부터 실험군별로 5-fluorouracil (30 mg/kg), 또는 mitomycin C (400 μg/kg)를 격일 간격으로 7회씩 투여하였다. 실험대조군은 암세포이식 후에 약제 대신 0.2mL의 생리식염수를 피부밑조직에 주사하였고, 정상대조군은 암세포를 이식하지 않은 동물을 사용하였다. 모든 실험군은 ether 마취하에 앞배벽을 열고 위조직을 절취하였으며, 통상적인 방법으로 전자현미경 표본을 만든 후 JEM 100CX-II 전자현미경으로 비교 관찰하였다. 5-fluorouracil 투여군의 으뜸세포는 수초구조가 다소 많이 관찰되는 이외는 대조군에 비해 큰 차이가 없었다. 그러나 mitomycin C 투여군의 경우는 핵이 농축되고 세포질의 전자밀도가 높고 과립세포질세망의 수조가 전체적으로 팽대되는 등 이미 괴사했거나 괴사중인 세포들이 자주 관찰되었다. 으뜸세포의 분비과립의 크기는 정상대조군, 실험대조군, 5-fluorouracil 투여군 및 mitomycin C 투여군의 경우 각각 0.98 (±0.108)μm, 1.05 (±0.092)μm, 0.94 (±0.123)μm 및 0.93 (±0.156)μm였다. 으뜸세포의 사립체의 크기는 정상대조군, 실험대조군, 5-fluorouracil 투여군 및 mitomycin C 투여군이 각각 0.80 (±0.130)μm, 0.83 (±0.143)μm, 0.87 (±0.165)μm 및 0.81 (±0.083)μm였다. 이상의 결과를 종합해보면 mitomycin C 또는 5-fluorouracil을 반복 투여하면 위점막 으뜸세포의 분비과립이 다소 작아지는 등 분비기능이 억제되었음을 시사하는 형태학적 변화를 보였으나 그 정도가 경미하였다. 특히 세포의 손상정도가 mitomycin C 투여군에 비하여 5-fluorouracil 투여군에서 더욱 경미하였으므로 5-fluorouracil은 위점막으뜸세포의 분비기능에 큰 손상을 주지 않는 것으로 생각된다.

다국어 초록 (Multilingual Abstract)

This experiment was performed to evaluate the morphological responses of the gastric chief cells of the mouse, inoculated with Ehrlich carcinoma cells in the inguinal area, following administration of 5-fluorouracil or mitomycin C. Healthy adult ICR mice weighing 25 gm each were divided into normal and experimental groups (experimental control group, 5-fluorouracil-treated group and mitomycin C-treated group). In the experimental group, 1×107 Ehrlich carcinoma cells were inoculated subcutaneously in the inguinal area. From next day after inoculations, 0.2mL of saline (experimental control group), 5-fluorouracil (30 mg/kg, 5-fluorouracil-treated group), or mitomycin C (400 μg/kg, mitomycin C-treated group) were injected subcutaneously to the animals every other day, respectively. The day following the 7th injection, animals were sacrificed. Pieces of the tissue were taken from the gastric mucosa, prefixed with 2.5% glutaraldehyde-1.5% paraformaldehyde solution, followed by post-fixation with 1% osmium tetroxide solution. The ultrathin sections were stained with uranyl acetate and lead citrate. The size of zymogen granule and the size of the mitochondrion in the gastric chief cells were observed and compared. In the 5-fluorouracil treated group, most chief cells did not show any difference in ultrastructure, except myelin figures were more frequently observed, in comparison with those of normal control group. But in the mitomycin Ctreated group, necrotic cells were more frequently observed than in normal control and 5-fluorouracil-treated group. The size of zymogen granule in the gastric chief cells of normal control, experimental control, 5-fluorouracil-treated and mitomycin C-treated groups were 0.98 (±0.108)μm, 1.05 (±0.092)μm, 0.94 (±0.123)μm and 0.93 (±0.156)μm, respectively. And the size of mitochondrion in the gastric chief cells of normal control, experimental control, 5-fluorouracil-treated and mitomycin C-treated groups were 0.80 (±0.130)μm, 0.83 (±0.143)μm, 0.87 (±0.165)μm and 0.81 (±0.083)μm, respectively. From the above results, in the treatment of low therapeutic doses of anticancer drugs into the animals inoculated with Ehrlich carcinoma cells, 5-fluorouracil may not suppress function of the gastric chief cells, but mitomycin C may exert a vicious influence on the function of the gastric chief cells.

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