The formation of radiation-induced DNA breaks: the ratio of double-strand breaks to single-strand breaks

Abstract

Ionizing radiation causes the formation of strand breaks in cellular DNA, as well as other types of lesions in the chromatin of cells. Some of the earliest investigations of the molecular basis of radiation-induced damage and the implications of enzymatic repair were done by Dr. H. S. Kaplan. The induction frequency of DNA double-strand breaks is of special importance, and it is of interest to know the relative proportions of single-strand and double-strand breaks. This ratio changes noticeably with the radiation quality (ionization density). Because it is difficult to assay for DNA lesions in the large mammalian genome, we have developed a method of assaying for DNA double-strand breaks in the supercoiled nucleosome-complexed Simian virus 40 (SV40) genome, irradiated intracellularly. In this communication we present our measurements of the DNA double-strand breaks (DSBs) to single-strand breaks (SSBs) ratio obtained from the intracellularly irradiated SV40 genome. After cobalt gamma ray and X ray irradiations, this ratio is about 1/10. Our methods and results are compared with pertinent data in the literature. If the DSBs/SSBs ratio of 1/10 for cellular chromatin is correct, a substantial number of DNA double-strand breaks are formed in a mammalian cell after moderate doses (1 Gy) of radiation. The implications of different types of DNA double-strand breaks are discussed.