Radiation-induced strand breakage in mammalian cell DNA. I. Enhancement of single-strand breaks by chemical radiosensitizers.

Abstract

SummaryChinese hamster cells irradiated with x-rays in complete medium while attached to glass surfaces and equilibrated with either air or nitrogen have been subsequently assayed for both colony-forming ability and size distribution of single-strand DNA fragments. Compounds evaluated for their ability to radiosensitize hypoxic cells and the concentrations used were: 1 mM para-nitroacetophenone (PNAP), 500µM N-(5-nitro-2-furfurylidine)-1-aminohydantoin (nitrofurantoin or NF2), 500µM 5-nitrofuraldehyde-2-semicarbazone (nitrofurazone or NF1), and 500µM 5-nitrofuraldehyde-2-oxime (nifuroxime or NF3). D0 values of 323, 227, 179, 155, 160, and 105 rads were obtained for N2, N2 + 1 mM PNAP, N2 + 500µM NF2, N2 + 500µM NF1, N2 + 500µM NF3, and air, respectively, which give enhancement ratios [ER(Survival)] of 1·00, 1·45, 1·80, 2·09, 2·01 and 3·08, respectively, for these conditions. The values of electron volt / single-strand break determined from alkaline sucrose sedimentation analyses for N2, N2 + 1 mM PNAP, N2 + 500µM NF2, N2 + 500µM NF1, N2 + 500μM NF3 and air were 284, 155, 109, 92, 82 and 83 which give enhancement ratios [ER(eV/SSB)] of 1·00, 1·83, 2·61, 3·08, 3·47 and 3·44, respectively. These data show that, within experimental error, the relative effectiveness of these compounds and molecular O2 as radiosensitizers of strand breakage in DNA of Chinese hamster cells is reflected at the level of cell survival.