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cis-Dichlorodiammineplatinum (II) 이 생쥐 폐포간중격의 미세구조에 미치는 영향

Effects of the cis-Dichlorodiammineplatinum on the Fine Structures of the Interalveolar Septum in the Mouse

Abstract

cis-Dichlorodiammineplatinum (II) (cis-Platin), a metallic compound, has widely been used as an effective anticancer chemotherapeutic agent. The precise mechanism of action of this agent is still unknown, but it is postulated that cis-Platin may act on the cancer cell like bifunctional alkylating agents. Although this agent is very beneficial to the patients with cervical cancer, germinoma of testis, neuroblastoma and others, it may also damage to the normal cell so that many side effects; severe hemorrhagic enterocolitis, bone marrow depression, renal damage and liver damage will develope. This experiment has been undertaken to pursue the cytotoxic effects of the cis-Platin on the ultrastructures of the interalveolar septum in the mouse lung. A total of 55 healthy male mice of ICR strain were used as experimental animals and divided into 5 mice of normal control group and 50 mice of cis-Platin treated group. The mice of cis-Platin treated group were sacrificed by carotid exsanguination at 6, 12, 24 hours, 3 days and 7 days after intraperitoneal injection of 6.0 mg of cis-Platin ($Abiplatin^R$ Abic Co. Ltd.) per kg of mouse body weight. The specimen obtained from the lower lobe of left lung were sliced into $1mm^3$ and prefixed with 2% glutaraldehyde -2.5% paraformaldehyde solution prepared with Millonig's phosphatae buffer solution (pH 7.4) at $4^{\circ}C$ for 3-4 hours. After postfixation with 1% osmium tetroxide solution all specimens were embedded in Epon 812. Ultrathin sections about $600-800{\AA}$ in thickness were stained with uranyl acetate and lead citrate and observed with Hitachi-600 electron microscope. The results obtained were as follows: 1. Local swellings with increase of electron density and number of pinocytic vesicles in the cytoplasms of the type I pneumocyte and endothelial cell of the blood air barrier in interalveolar septum of cis-platin treated mice were observed. 2. Cisternae of rough endoplasmic reticulum were dilated and sacculated in association with detachment of membrane bound ribosomes of the type II pneumocyte in interalveolar septum of cis-Platin treated mice. 3. Swollon mitochondria with uneven electron density of their matrix were observed in the type II pneumocyte of interalveolar septum in the cis-Platin treated mice. 4. The lamellae of lammelar bodies in type II pneumocyte of interalveolar septum in cis-Platin treated mice were devoided or transformed into homogeneous electron dense material. It is consequently suggested that cis-Platin would induce the cellular edema of type I pneumocyte and endothelial cell, and degenerative changes of cytoplasmic organelles of the type II pneumocyte in the interalveolar septum of the mouse lung.

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