Identification of human in vitro cell lines with greater intrinsic cellular radiosensitivity to 62.5 MeV ( p → Be+) neutrons than 4 MeV photons

Abstract

Purpose : To identify human in vitro cell lines with a high relative cellular sensitivity to fast neutrons as compared to photons and to examine their relationship to intrinsic photon radiosensitivity and cellular proliferation kinetics. Methods and Materials : The clonogenic cell survival following exposure to low LET, 4 MeV photons or, high LET, 62.5 MeV (p → Be +) fast neutrons and the cell kinetic parameters of 30 human in vitro cell lines, covering a wide range of histologies, were analyzed alone and with previously published data of Fertil and Malaise. The relative survival at 1.6 Gy of neutrons (SF 1.6) compared to 2 Gy of photons (SF 2) (the doses per fractions used in the Clatterbridge fast neutron studies) and the cell kinetic parameters of the 30 cell lines were also compared. The relative lethality of 62.5 MeV fast neutrons was assessed by comparing the ratio α neutrons/α photons to α photons or SF 1.6 neutrons/SF 2 photons to SF 2 photons. Cellular proliferation kinetics were measured by flow cytometry following BrdU incorporation and the relationship of cellular proliferation to relative neutron lethality was measured by comparing the α neutron/α photon ratio to the labelling index (LI), potential doubling (T pot) and ploidy. Results : The majority of cell survival curves obtained following exposure to 62.5 MeV fast neutrons were curvilinear with beta values of similar order to those obtained with low LET 4 MeV photons. Comparison of alpha values for neutrons and photons revealed a relatively neutron sensitive subset of 9 out of 30 in vitro cell lines. This subset was not, however, distinguishable when 1.6 Gy of neutrons was compared to 2 Gy of photons. There was no correlation between cell survival with neutrons or photons and the cell kinetic parameters T pot or LI or with DNA ploidy. Conclusion : The use of in vitro assays of neutron and photon radiosensitivity irrespective of cell kinetic parameters allows identification of neutron sensitive cell populations when the ratio of the α values for neutrons and photons is compared to the reciprocal of the α photon value. This relationship is not apparent when fractions of 2 Gy of photons are compared to 1.6 Gy of neutrons. Whether or not this identification can be borne out in fractionated regimes in the clinic remains to be proved.