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[Cancer Research 35, 932-938, April 1, 1975]
© 1975 American Association for Cancer Research

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Repair of Radiation Damage in Lewis Lung Carcinoma Cells following in Situ Treatment with Fast Neutrons and {gamma}-rays1

William U. Shipley2, Judith A. Stanley, V. Doreen Courtenay and Stanley B. Field

Department of Biophysics, Institute of Cancer Research, Sutton, Surrey [W. U. S., J. A. S., V. D. C.], and Medical Research Council Clyclotron Unit, Hammersmith Hospital, London [S. B. F.], England

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: D0 = 111 rads, Dq = 342 rads, n = 22 for {gamma}-rays, and D0 = 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, D0 = 315 rads for {gamma}-rays and D0 = 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 after {gamma}-ray but not after neutron irradiation. Repair of potentially lethal 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.

1 The work contained in this report was partly supported by National Cancer Institute Contract NCI-CM-23717.

2 Work in this report done while on a Moseley Fellowship from Harvard Medical School, Boston, Mass. Present address: Department of Radiation Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Mass. 02114.

Received 8/12/74. Accepted 12/20/74.




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Overcoming Physiologic Barriers to Cancer Treatment by Molecularly Targeting the Tumor Microenvironment
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Copyright © 1975 by the American Association for Cancer Research.