“Small Clones” in Irradiated Tumour Cellsin vivo. Kinetics of re-growth of murine leukaemia cells surviving irradiation with X rays, fast neutrons and accelerated charged particles

The growth of the intraperitoneally injected P–388 lymphocytic leukaemia cells until they cause the death of isologous recipient mice has been studied in vivo, with unirradiated cells and with cells surviving after irradiation under anoxic conditions with X rays, fast neutrons and accelerated charged particles. Maximum delay in re-growth of tumour cells after irradiation occurs when re-growth takes place from the smallest possible number of surviving cells. The fact that this delay in re-growth can exceed the mean time from inoculation of one unirradiated tumour cell to death of the recipient animal strongly suggests a reduction in the growth rate of some surviving cells analogous to the formation of “small clones” after irradiation of mammalian cells in vitro. The rate of re-growth of tumour cells surviving fast neutron irradiation of intermediate LET (14 MeV monoenergetic neutrons and 6 MeV cyclotron-produced fast neutrons) is no more rapid than that of tumour cells depopulated to the same degree by irradiation with low-LET X rays and accelerated charged particles; in fact the intermediate- LET fast neutron irradiation appears to produce a slightly higher percentage of slowly growing tumour cells among those which survive. The RBE for tumour re-growth after irradiation with fission-spectrum (high-LET) fast neutrons is only slightly lower than the RBE of the same radiation for producing cell reproductive death.