Kinetics of Depopulation, Repopulation and Host Cell Infiltration in the Rhabdomyosarcoma R1H After 14 MeV Neutron Irradiation

The kinetics of depopulation and repopulation of the solid transplantable rhabdomyosarcoma R1H in the rat was studied following irradiation with 5 Gy of 14 MeV neutrons. Several parameters were sequentially measured over a time period of 4 weeks after irradiation: the tumour volume was assessed by in situ caliper measurements; the numerical density of tumour cells was obtained by morphometry; the clonogenic fraction of tumour cells was derived from in vitro colony assay; and the numerical ratio of host to tumour cells was determined by flow cytometry. From these primary parameters the number of clonogenic tumour cells, non-clonogenic tumour cells, and nucleated host cells per tumour, as well as their variation with time, were derived. The results were compared with two sets of data obtained previously for the same tumour exposed to 15 Gy of 200 kVp X-rays. Survival of tumour cells was reduced to 5·5 ± 0·5% by 5 Gy neutrons and to 4·5 ± 0·5% by 15 Gy X-rays, i.e. an RBE of close to 3. There was a lag period before the onset of repopulation (4·9 ± 0·4 days and 4·9 ± 0·5 days, respectively), followed by a high initial rate of repopulation corresponding to a doubling time of 2·0 ± 0·2 days for neutrons and 2·1 ± 0·2 days for X-rays. The rate of depopulation was significantly different for the two treatment modalities; the halving time for the number of non-clonogenic tumour cells was 11 ± 4 days for neutrons and 2·8 ± 0·5 days for X-rays. The number of host cells per gram of tumour tissue increased with time after irradiation up to 5-fold. However, after neutron irradiation the host cells accumulated more slowly and reached a maximum value by day 12 as compared to day 7 for X-rays. It is concluded that the lower rate of accumulation of host cells, which consist mainly of mononuclear phagocytes and granulocytes, might be the cause for the lower rate of depopulation observed after neutrons as compared to X-rays.