The authors studied the activation effect in vitro of polyanionic mitogen-polyacrylic acid (PAA) on several types of mouse lymphocytes. The action of PAA was evaluated from an early effect on membrane (Na+, K+)- and Ca2+-ATPases. PAA was demonstrated to interact with the membrane of B cells from the spleen and immature T lymphocytes from the thymus, producing no effect on mature T cells from the spleen. The lack of the PAA effect on mature T lymphocytes was found to be linked with high density of negatively charged groups on the surface of these cells. Artificial lessening of the density of the negatively charged groups by the cleavage of the terminal N-acetylneuraminic residues with the aid neuraminidase leads to the change of mature T cells into PAA-sensitive ones.
The paper is concerned with a study of the molecular mechanisms responsible for activation of B lymphocyte division by polyanions, polyacrylic acid (PAA) and dextran sulfate (DS). The mitogenic doses of PAA and DS were discovered to provoke an early increase in lymphocyte plasma membrane permeability. The cell membrane permeability for K+, Ca2+ and for labeled thymidine and uridine was measured in murine spleen cultures in vitro The K+ outflow from the cells was recorded according to variation in K+ concentration in the extracellular medium with the aid of a selective valinomycin electrode. The intensity of cell penetration by exogenous 45Ca, 3H-uridine or 3H-thymidine was determined by radioindicator analysis of the cytoplasma isotope pool. One to 2 min after adding the mitogenic doses of PAA or DS, the K+ outflow from lymphocytes markedly increased. It has been proved that this effect is not connected with inhibition of Na+, K+-ATPase of the plasma membrane. The increased membrane permeability for 45Ca and 3H-uridine was recorded 30-40 min after lymphocyte activation with the polyanion, that for 3H-thymidine was seen later (after 4-6 h). It is assumed that the differences between the time of recording high accumulation in the cytoplasm of 45Ca, 3H-uridine and 3H-thymidine and the time of recording high outflow of K+ from lymphocytes are determined by the differences in the sensitivity of the methods applied.
A dynamic study of histological preparations of a Brown-Pearce tumor, transplanted in rats, indicated that initial signs of tumor regression commence from the 15th day and complete death of tumor cells is noted by the 40th–65th post-transplantation day. In view of the abovesaid the transplantation of tumors by this method is possible in a number of generations even on the 10th–12th day after heterotransplantation. Notwithstanding good tumor vascularization and the presence of tumor thrombi in the vessels, necrosis and death of the cells occur by the 40–65th day. A prevalence of lymphoid infiltration is observed in the areas where the changes of the tumor cells are marked.
One of the most important problems in experimental oncology is tumor heterotransplantation. The authors developed a method for transplanting rabbit Brown-Pearce tumors to rats. Heterogenic tumors were thus obtained in rats. By the 16th–29th day after inoculation their weight was from 10 to 20 gm. Later on slow resolution of the tumor occurred, lasting for 1.5–2 months and more; this enabled them to study dynamic changes of its biological and biochemical properties. The tumor was maintained in a number of generations of previously prepared rats, as well as by its transplantations from the prepared rats to the healthy ones. The tumor taken in the prepared rats constituted 70%. When transplanted to rabbits Brown-Pearce tumor developed in generations of rats retains its primary properties.