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Quantitative cellular assays of the transplantability of 19 spontaneous reticulum cell sarcomas (RCS) of the BC3F1mouse were carried out by injecting serial dilutions of monodispersed cells into syngeneic hosts through the intravenous, intracranial and subcutaneous routes. A clear relationship was found between the size of the inoculum and the incidence of tumor takes by all routes, but even for inocula of 5 million cells only 13 tumors grew in one or more of the transplanted recipients. The intravenous route of injection was found to be the most effective, both in terms of the absolute number of tumor takes and the number of cells necessary to produce a given level of takes. The survival of the animals injected intravenously was related to the number of cells received in that earlier deaths occurred with the most concentrated cell suspensions. Attempts to transmit the tumor by cell-free extracts injected into newborn or 1-month-old syngeneic hosts failed to substantiate the possible presence of a specific leukemogenic agent.

The ultrastructure of T and B lymphocytes has been examined in long-term syngeneic chimaeras and age-control mice. Spleen cell suspensions from these mice were passed through glass wool columns to obtain pure lymphocyte populations. These cells were then separated into T and B lymphocytes by nylon wool columns, and their purity was tested by cytotoxicity assays with anti-ϑ serum. Electron microscopic observations on such separated T and B lymphocytes did not reveal morphological differences except when the cells were fully differentiated, either as mature (T2) cells or plasmacells. In particular, T2cells showed a very high cytoplasmic density, attributable to the presence of a larger number of microfilaments with respect to immature (T1) cells. In long-term chimaeras a significantly larger number of T2cells was found as compared to age-control mice, and this morphological observation is correlated with the differences in immune reactivity and leukemia incidence previously described in these mice.

Life-long observations on untreated animals have shown that spontaneous reticulum cell sarcomas (RCS) developed in 56.5 % male mice of the hybrid (C57BL/Cne x C3H/Cne) F1strain; the average age at death of mice with tumors was 949 days, compared with 929 days for all causes: no age-specific peak of mortality has been shown to occur over the entire life span of the animals. Histologically, the spleen and all the lymphnodes, including the mesenteric node, were always invaded; neoplastic growth was found less frequently in kidneys, liver and lungs (77, 70, and 40%, respectively), only occasionally in other organs such as adrenals and testes, and never in the thymus. The tumor was predominantly composed of a single type of neoplastic cells, resembling highly undifferentiated reticular cells, typically proliferating from the periarteriolar region of the lymphatic follicles in the spleen. The monomorphic aspect of the tumor cell population suggests that RCS in this strain of mice may be classified as type A according to Dunn. Electron-microscopy observations showed the presence of a few virus-like particles both in tumor cells and in sediments from cell-free extracts. Transplantation of cells from spontaneous RCS into both normal and lethally-irradiated syngeneic recipients was successful only in 4 out of 7 experiments, regardless of the tissue of origin of the neoplastic cells (spleen, lymphnodes or bone marrow). Virus-like particles were seen with higher frequency in transplanted tumors. Inoculation of cell-free extracts into neonatal mice of low-leukemia strains has not so far been successful. Splenectomy of young animals as well as the intravenous injection of syngeneic bone marrow cells immediately following a lethal dose of whole-body X-irradiation significantly reduced the frequency of spontaneous tumors.