Some cytological effects of carzinophilin on the MTK-sarcoma III
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The present article deals with some cytological effects of carzinophilin on the tumor cells of the MTK-sarcoma III, a transplantable rat ascites tumor, with particular regard to the morphological response of the tumor cells to the drug. Intraperitoneal injections at the dose levels of 1000, 2500 and 5000u/Kg were made in tumor-bearing rats on the 3rd day of transplantation.In the application of a dose tolerated, it was found that carzinophilin attacked initially interphase cells inducing in various ways damage to cells with mitotic distur 1-1 bances. The predominant patterns of response are as follows:The morphological deformations of nucleoli are most remarkable in affected cells. The nucleoli show irregular thread-like processes or atypical amoeboid protrusions like pseudopodia. The advanced damage is evidenced by the vacuolization of nucleoli. The agglutination of the chromosome threads into several clumps inside the nuclear membrane is also a degenerative change common in affected cells. These cells seem to undergo disintegration without showing mitotic division. Metaphase block is also produced at every dose level. The drug exerts also a destructive effect on the cytoplasm; it induces a blebbing of the cell surface and cytoplasmic swelling, and in a more advanced condition there is a formation of vacuoles in the cytoplasm. The majority of affected cells seems to undergo degeneration. Meanwhile, some of the cells under influence seem to proceed to the metaphase stage, but they are damaged by subsequent mitotic aberrations such as chromosome breakage, bridge formation and anaphase lagging.Generally the severity of response seems to increase with increased concentration of the drug. The therapeutic effect seems to be expected by separate and repeated applications of the drug at a tolerant dose level, as evidenced by a considerable prolongation of life of tumor-bearing animals.Upon exposure to carzinophilin, most of the tumor cells were damaged, while certain of them characterized by a small amount of cytoplasm and well-defined compact nuclei remained unaffected by the action of the drug. These persistent unaffected tumor cells constitute the primary source of the subsequent growth of tumor, leading to the reappearance of the tumor in the treated animals. Detailed observations revealed that the chromosome complex of these cells was essentially similar to that of the stemline-cells of this tumor. It is therefore the unaffected tumor stem-cells that participate in the renewed growth of the tumor.
- 日本遺伝学会の論文
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