“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

Abstract

The growth of the intraperitoneally injected P-388 lymphocytic leukemia cells until they cause the death of isologous recipient mice was 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 tumor 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 1 unirradiated tumor 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 tumor cells surviving fast neutron irradiation of intermediate LET [linear energy transfer] (14 MeV monoenergetic neutrons and 6 MeV cyclotron-produced fast neutrons) is no more rapid than that of tumor 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 tumor cells among those which survive. The RBE [relative biological effectiveness] for tumor 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.