Studies of the dissemination and quantitative transplantation of a lymphocytic Leukaemia of CBA mice

Abstract

1. Differences are described between the pathological findings in a CBA mouse with spontaneous lymphocytic leukaemia and those in CBA mice to which the leukaemia was subsequently transplanted. The significance of these differences is discussed in relation to genesis of the leukaemia in the original mouse. 2. The typical course of the transplanted disease is described with particular reference to the changes in the circulating leucocytes. 3. Signs of severe disturbance of the central nervous system, occurring in one-quarter of the mice bearing the transplanted disease, were associated with foci of degeneration in the cerebellum; no malignant infiltration of the brain was observed. No evidence of an associated neurotropic virus infection was obtained. 4. The malignant cells resembled the larger cells of the normal thymus gland. The diameters of the malignant cells gave a characteristic frequency distribution curve which was readily distinguishable from that of the nucleated cells released from normal organs suach as the spleen, thymus or lymph gland. The construction of such curves provided a means of demonstrating the degree of replacement by malignant cells in lymphoid tissue. 5. After injection of malignant cells into the peritoneal cavity, there was an initial increase in the number of malignant cells in the cavity but this did not progress and no ascites tumours were produced. Solid tumours were not seen after the subcutaneous injection of malignant cells. 6. After the intraperitoneal injection of 105 malignant cells, transplantable malignant cells were not demonstrated in the blood, lungs or axillary glands of the injected mice until at least 1 week after injection. 7. The mean survival time of mice injected with malignant cells was not modified by splenectomy three days before, or by administration of cortisone or the injection of large numbers of radiation-killed malignant cells after, the injection of viable malignant cells. 8. A method is described for the " titration " or bioassay of suspensions of viable malignant cells, the results of a titration being expressed as the TD50, that is the number of apparently viable malignant cells required to convey leukaemia to 50 per cent of a group of injected mice. The TD50 values obtained in 6 separate intraperitoneal titrations of cells derived from leukaemic livers varied from 0 7 to 3 0 cells (mean, 2-0 cells). The following factors had no significant influence on the TD50 values: the route of injection of the cells (intravenous, intraperitoneal or siabcutaneous); storage of the cells for 8 hours at 0-2°C. before injection; or the source of the leukaemia cells (leukaemic liver or blood). 9. The leukaemia was not transplantable to adult mice of a heterozygous albino strain but was successfully transplanted to a proportion of the albinos by their injection in utero. 10. The results of several experiments, including the injection of centrifuged extracts of leukaemic tissues into CBA mice in utero, provided no evidence of cell-free transmission of the leukaemia. I am indebted to Mrs. Dorothy Levy for her skilled technical assistance, and to Dr. P. Hansell and the Department of Medical Photography, Westminster Hospital for the photomicrographs. I am grateful for grants from the British Empire Cancer Campaign, during tenure of which this work was done. © 1958, The British Empire Cancer Campaign for Research. All rights reserved.