Development of necroses, virus activation and giant cell formation after treatment of Ehrlich ascites tumor with metallocene dichlorides.

Light-microscopic and ultrastructural alteration patterns are investigated after in vivo treatment of EAT with the cytostatic agents VDC and TC. Both substances induce mitotic aberrations, e.g., pyknotic metaphases, lagging chromosomes during anaphase, and multipolar mitotic figures. The appearance of mononucleate and, occasionally, multinucleate giant cells is observed mainly 48--96 h a.t. The first observable ultrastructural changes are seen within the nucleus and consist of chromatin condensation and the enlargement of the nuclear surface. Thereafter, VDC induced morphological signs of unbalanced cellular growth, whereas TDC and DDP cause the development of necroses of the tumor cells, the phagocytosis of the damaged cells by macrophages, and, in consequence, complete tumor regression. Some hours after application of TDC, the formation of type-A-virus particles can be recognized. It is supposed that the apparent virus induction acts as a fortifying factor in the course of tumor inhibition by TDC.