Cytokinetic Control Mechanisms in Ehrlich Ascites Tumour Growth

Ehrlich ascites tumour in mice was studied as a model system to elucidate the cytokinetic mechanisms controlling growth of cell populations. The basis for a retardation in growth rate during tumour development was determined with the aid of 3H-thymidine labelling and autoradiography. Three possible cytokinetic variables in growth regulation, namely, duration of the mitotic cell cycle, fraction of the cycling cells in the population (growth fraction) and rate of cell loss, were measured at different stages of growth. It was concluded that a deceleration in growth was a result of (1) a gradual prolongation of the cell cycle and its components and (2) a progressive decline in the growth fraction. Rate of cell loss did not appreciably change during most of the growth. It was also found that the total cell mass rather than the tumour age dictated the growth rate at any instant over a considerable range of growth. Non-cycling cells were found to resume cycle when a fraction of an old tumour was transplanted in new hosts, 3H-thymidine labelling combined with microspectrophotometric estimates of cellular DNA was utilized to locate the stages at which a cell cycle could be suspended or resumed. It was found that decycling or recycling could occur only after mitosis and before DNA synthesis; non-cycling (G0) state resembled G1, which was absent in the proliferating tumour cells. These findings are relevant to a further understanding of the molecular events leading to the initiation or suspension of a cell cycle. They are also pertinent to formulating a rationale for tumour therapy — for example with radiation — when coupled with the existing knowledge of the relative sensitivity of cells at different stages of cycle. (author)