A Survival Curve for Mammalian Leukaemia Cells Irradiated 'in vivo (Implications for the Treatment of Mouse Leukaemia by Whole-Body Irradiation)

Abstract

BARNES, Corp, Loutit and Neal (1956), in a preliminary report, described the successful eradication of murine leukaemia by treatment of leukaemia-bearing mice with whole-body radiation followed by intravenous isologous bone marrow.Attempts by us to cure a similar leukaemia in the same strain of mouse using similar methods and a larger dose of radiation have not been successful. It appeared that the prospects of eradicating leukaemia by this form of treatment might be usefully explored by determining a survival curve for leukaemia cells irradiated in vivo. Given data concerning the number of leukaemia cells in a mouse at the time of treatment, such a curve would enable the chance of cure by a specified dose of whole-body radiation to be predicted. This paper reports the determination of a survival curve of this kind. We believe that the curve will be of considerable general interest because we are not aware of a survival curve for mammalian cells irradiated in vivo having been described previously. An unsuccessful attempt to cure leukaemia-bearing mice by whole-body radiation is analysed in the light of the data provided by this curve. MATERIALS AND METHODSMice.-The CBA mice used in all the experiments were bred by brother-tosister mating in this laboratory and were aged 2-6 months when used for experiment.Leukaemia strain.-The lymphocytic type of leukaemia arose spontaneously in a mouse of the same colony as that providing the mice used in the experiments, and no evidence of a genetic difference between the malignant cells and the host mice has been detected in a wide range of experiments which could have revealed such a difference. A detailed account of the leukaemia, and of the method of bioassay used to measure the number of viable leukaemia cells in a suspension, appears elsewhere (Hewitt, 1958). Briefly, the method of bioassay is as follows: a single-cell suspension of leukaemia cells is prepared from the infiltrated liver of a leukaemic mouse; the density of morphologically intact leukaemia cells is determined by counting in a counting chamber under phase-contrast microscopy, and accurate serial dilutions of the counted suspension are made; the mean number of leukaemia cells in 0-2 ml. volumes of each of the series of dilute suspensions is calculated from the cell density of the initial suspension and the dilution factor; 0.2 ml. volumes of each of a series of selected dilutions are injected intraperitoneally into a group of 6-10 mice; the incidence of leukaemia in each injected

Cytological Demonstration of the Clonal Nature of Spleen Colonies Derived from Transplanted Mouse Marrow Cells

“…It was therefore desirable to prove whether or not spleen colonies each develop from single cells and hence are clones; for if they are, it would be possible to study clonal populations of haematopoietic cells in vivo. Evidence from previous experiments supporting the view that the colonies are clones is as follows: (1) the curve relating the number of nucleated marrow cells that are transplanted to the number of colonies that develop in the spleen is linear, and shows no initial threshold 1,2 ; (2) the radiation survival curve of cells that can form colonies closely resembles the survival curves obtained for single cells in cell culture 4 or tumour transplants 5 . These observations provide only indirect evidence that the colonies are clones.…”

Non-Targeted Radiation Effects in Radiotherapy &Roles of Radiation-Induced Genomic Instability and of the Bystander Effect in Cancer Cure by Radiotherapy

“…When the tumour cells were irradiated before transplantation, more cells were needed for successful transplantation; however, the shape of the curve still followed a Poisson distribution, suggesting the interpretation that, again, a single cell that survived irradiation, while the others were sterilized, was the origin of the successful tumour transplant. In plotting the negative logarithm of the number of tumour cells for a 50% success rate against radiation dose, Hewitt (3), and later Berry (4) and several others, produced dose -effect curves that resembled those published a few years earlier by Puck for colony forming cells in vitro (5). This was interpreted by Gray (6) as indicating that both effects, i.e.…”

“…The results of these experiments, however, are at odds with a large number of older studies investigating the effect of radiation-sterilized tumour cells on the clonogenicity of tumour cells in vitro and in vivo. Some of the earliest were performed by Hewitt (3). All published experiments have demonstrated that radiation-inactivated tumour cells do not kill bystanding tumour cells.…”

Modality comparison for small animal radiotherapy: A simulation study

“…4) when total body irradiation of mice was performed with a 60 Co unit. Other total body rat irradiations followed, using either radioactive nuclides [5][6][7] or x-ray tubes 8,9 as sources of radiation.…”