Restriction Endonuclease- and Radiation-Induced DNA Double-Strand Breaks and Chromosomal Aberrations: Similarities and Differences

Abstract

It is a characteristic of ionizing radiations that the energy per absorption event is greatly in excess of the energy required to dissociate covalent bonds. In an irradiated cell, therefore, damage can occur at any point in the structure of DNA. As a result of this high energy per ionizing event, radiation is able to induce a variety of lesions in the DNA of cells which can be grouped into those involving damage to the base moeity without breakage of the sugar-phosphate chain (base damage), cross-links (DNA-DNA and DNA-protein) and those involving breakage of one or both strands of the double helix (single- and double-strand breaks respectively). Accumulating evidence points to the double-strand break (dsb) as the major lesion in causing cellular, chromosomal, mutagenic and oncogenic effects of ionizing radiation. It is for example, quite characteristic of ionizing radiation and certain chemical agents (e.g. bleomycin) that they induce chromosome aberrations at first mitosis following exposure of a cell in the G1 phase of the cell cycle, whereas agents such as UV that induce almost entirely single-stranded lesions (principally thymine dimers, which are converted to single-strand breaks during repair) only chromatid aberrations are seen, resulting from misreplication of DNA during S-phase. Furthermore, derived mutants of mammalian cells which are deficient in the repair of dsb show a high chromosomal sensitivity (Kemp and Jeggo 1986; Darroudi and Natarajan 1987; Bryant et al. 1987).