Repair of radiation damage in Lewis lung carcinoma cells following in situ treatment with fast neutrons and gamma-rays.
Lewis lung tumor cells were irradiated with 60Co gamma-rays or cyclotron-produced neutrons in situ as solid s.c. tumors or in vitro as single cell suspensions. Cell survival was assayed by colony formation both in vitro in soft agar and in the lungs of isogeneic recipient mice. Survival curve characteristics measured in vitro were: Do = 111 rads, Dq = 342 rads, n = 22 for gamma-rays, and Do = 61 rads, Dq = 46 rads, n = 2 for neutrons. In situ, the hypoxic fraction was 0.36. Irradiation in situ gave, for the hypoxic subpopulation, Do = 315 rads for gamma-rays and Do = 91 rads for neutrons. The oxygen-enhancement ratio for gamma-rays was 2.8 and for neutrons was 1.5. Using the split-dose technique, in which two equal doses were administered, separated by 4 hr chronically hypoxic tumor cells repaired sublethal damage, assayed by leaving tumor cells in situ up to 24 hr posttreatment, could not be detected after neutrons, but after gamma-rays it was observed as a 3- to 6-fold increase in survival. The repair of potentially lethal damage increased the relative biological effectiveness of neutrons from 3.7 at a survival level of 5% when assayed immediately after treatment to 4.7 when assayed 6 to 24 hr after treatment. These observations, primarily limited to the chronically hypoxic subpopulation of tumor cells, suggest that decreased repair of potentially lethal damage as well as sublethal damage may be an important radiobiological difference between the effects of high and low linear energy transfer radiation.
D000818:Animals; D002470:Cell Survival; D002999:Clone Cells; D003037:Cobalt Radioisotopes / Q000627:therapeutic use; D005214:Fast Neutrons / Q000627:therapeutic use*; D005260:Female; D008175:Lung Neoplasms / Q000532:radiotherapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000532:radiotherapy; D009502:Neutrons / Q000627:therapeutic use*; D011830:Radiation Effects; D011879:Radiotherapy Dosage
D003037:Cobalt Radioisotopes