The radiobiology of DNA strand breakage.

Abstract

The yield of single-strand breaks in lambda DNA within lysogenic host bacteria was measured after exposure to 4-MeV electrons (50 msec) and rapid transfer (45 msec) to alkaline detergent. In nitrogen anoxia the yield was 1.2 X 10(-12) DNA single-strand breaks per rad per dalton, and under full oxygenation the yield increased to 5 X 10(-12) breaks per rad per dalton. A search for the presence of fast repair of strand breaks operating within a fraction of a second. Strand breaks produced in the persence of oxygen were repaired in 30-40 sec, while breaks produced under anoxia were rejoined even slower. A functional product from the po[A] gene was needed for the rejoining of the broken molecules. Intermediate levels of DNA strand breakage seen at low concentrations of oxygen are dependent on the concentration of cellular sulfhydryl compounds, suggesting that in strand breakage oxygen donors compete for reactions with radiation-induced transients in the DNA. Intercomparisons of data on radiation-induced lethality of cells and single-strand breaks in episomal DNA allow the distinction between two classes of radiation-induced radicals, R-1 and R-2, with different chemical properties; R-1 reacts readily with oxygen and N-oxyls under formation of potentially lethal products. The reactivity of oxygen in this reaction is 30-40 times higher than that of TMPN. R-2 reacts 16 times more readily that R-1 with oxygen under formation of single-strand breaks in the DNA. R-2 does not react with N-oxyls.