High Resolution Gel Electrophoresis Methods for Studying Sequence-Dependence of Radiation Damage and Effects of Radioprotectants in Deoxyoligonucleotides

Abstract

Ionizing radiation is known to produce both single and double-strand breaks in DNA (von Sonntag et al., 1981; Hutchinson, 1985; Ward, 1988). In aqueous DNA solutions, radiolysis of water produces OH radicals which react with DNA bases and sugar residues; hydrogen atom abstraction from the sugar moieties produces radicals which ultimately give rise to strand scission. In the case of low LET radiation (e.g. γ-irradiation), DNA damage caused by OH- radicals generated in the bulk of the aqueous solution is called the “indirect effect” (see for example, Skov, 1984; Achey and Durea, 1974; van Rijn et al., 1985; Roots et al., 1985; Siddiqi and Bothe, 1987; Schulte-Frohlinde, 1989). In the case of high LET radiation, e.g. charged heavy particles, a direct deposition of energy within the DNA molecules is dominant in producing DNA damage by the “direct effect” (see Holley et al., 1990, for example). The formation of DNA strand breaks, in particular double-strand breaks, are rather strongly correlated with ionizing radiation-induced cell killing (Coquerelle, 1978; Elkind, 1985). Other harmful effects of ionizing radiation (Beebe, 1982), including mutations (Waters et al., 1991; Jaberaboansari et al., 1991; Raha and Hutchinson, 1991; Geacintov and Swenberg, 1992) have been well documented.