The present paper deals with some cytological effects of triethylene thio-phosphoramide (thio-TEPA or 'Tespamin', SUMITOMO Co.), a derivative of ethyleneimine compounds, upon tumor cells of the transplantable ascites tumors of the rat (MTK-sarcoma III) and mouse (EM-tumor), with particular regard to mitotic abnormalities induced by the drug. Intraperitoneal injections of the drug at dose levels of 1mg/kg, 2mg/kg and 5mg/kg were made in tumor-bearing animals on the 4th day of transplantation.
By the application at a dose of 1mg/kg in the MTK-sarcoma III, thio-TEPA exerted a destructive influence upon interphase cells with a considerable increase of cell-volume and morphological deformation in various ways. At the same time, there was a marked decrease in mitotic rate of the tumor cells. Predominant patterns of abnormalities induced in tumor cells are: the formation of micro-nuclei and multi-lobated nuclei, the reduction in stainability of the cytoplasm and nucleus, the swelling of the cytoplasm, and the formation of vacuoles in the cytoplasm.
Damaging effects of the drug on the chromosomes were also remarkable. Fragmentation and translocation of chromosomes were rather common at metaphase. In addition, the formation of bridges and heavy stickiness of chromosomes were usual in treated tumor cells at ana- and telophase. Basing on the results of present study by means of the Feulgen reaction, it is suggested that the mitotic abnormalities induced by the drug may be caused by the disturbance of the nucleic acid metabolism in the interphase nucleus.
It was found that some of tumor stem-cells infiltrated in the omentum have remained alive unaffected by the drug. It seems probable that they form a primary source for regrowth of the tumor by their proliferation.
View full abstract