THE principal object of studies of the cell population kinetics of tumours is to explain how a tumour attains its particular growth rate, and thus to make a more informed judgement on methods of growth control. The growth rates of tumours show wide variations, both between and within individual species. In man, volume doubling times for primary and secondary lung tumours range from about two weeks to many months (Steel and Lamerton, 1966); in experimental animals, spontaneous tumours with volume doubling times of a few days are common and under repeated transplantation doubling times of less than 24 hours can be attained. The problem is to identify the proliferative characteristics of the cell populations which have such widely different growth rates.Such a problem must necessarily be treated as one of comparative biology. Our ultimate aim is an understanding of the growth rate of tumours in man, but the limitations imposed by experiments on human beings rule out at present a thorough analysis of the cell population kinetics of human tumours. The scope for experiment on animal tumours, particularly transplanted tumours, is much greater. What must be done therefore, is to look first at the simplified cases provided by experimental tumours, and then to extend the investigations to tumours that are progressively closer to the human counterpart.The approach in the present work has been to analyse by a variety of techniques the cell population kinetics of tumours of known growth rate, in order to find the extent of agreement between them and to characterise, as far as possible, the state of proliferation of the tumour cell population. A similar approach has been used by Mendelsohn (1965). Great importance is attached to the simultaneous measurement of volume doubling time, for whether measurements of cell proliferation are consistent with the overall tumour growth rate is the conclusive test of their significance.The growth rate of a tumour is the resultant of cell production and cell loss (Fig. 1). Cell loss is an extremely difficult parameter to measure (Steel, 1966) and there are at present no direct methods by which it can be estimated; cell loss would, however, be indicated by a discrepancy between total cell production rate and overall growth rate. The state of cell proliferation in a tumour is best specified by a distribution of cell cycle times, this being taken to include both the distribution for proliferating cells as well as information on the fraction of cells which are essentially non-proliferating. The distribution of cell cycle times may or may not take a standard mathematical form. In the more heterogeneous tumours, the fact that the availability of nutrients to different regions may vary widely, some regions showing various degrees of starvation, suggests that a

Summary.-The formation of lung colonies by i.v. injected Lewis lung-tumour cells in syngeneic recipients was greatly enhanced by prior treatment of the mice with cyclophosphamide. The lung-cloning efficiency was linearly related to cyclophosphamide dose and the optimum time of treatment was 2-4 days before the injection of tumour cells. The resulting lung colonies had a similar size distribution to colonies in untreated recipients. Bleomycin, local thoracic irradiation and wholebody irradiation were much less effective in enhancing the lung-cloning efficiency.Cyclophosphamide also enhanced the take probability of i.m. implanted tumour cells.

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C57Bl mice were treated with thoracic irradiation to doses in the range 12.0 to 18.9 gray. Few deaths were observed in the period 80--160 days after irradiation (an end-point of lung damage used by other investigators) and the median survival times ranged from 200 to 310 days. CBA mice treated under identical conditions predominantly died between 80--160 days and it is therefore concluded that C57Bl mice show unusually prolonged survival following this treatment. Six chemotherapeutic agents were given to C57Bl mice together with thoracic irradiation, in most cases two weeks beforehand. Adriamycin, bleomycin and cyclophosphamide enhanced the mortality of the mice. Most agents had little effect on radiation-induced skin damage.

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