The Level of Induced DNA Double-strand Breakage Correlates with Cell Killing after X-irradiation

Abstract

The neutral filter elution technique has been used to examine the relationship between X-ray-induced DNA double-strand breakage (dsb) and lethal lesions. The ratios of the different lesions produced by X-irradiation were varied by irradiation in the presence of different radiomodifiers, and in each case the same linear relationship between lethal lesions and induced DNA dsb was found. This relationship also held for cells given a hyperthermic treatment before irradiation. It is concluded that DNA dsb is probably the lethal lesion induced by ionizing radiation.

The effect of 2-[(aminopropyl)amino] ethanethiol (WR-1065) on radiation induced DNA double strand damage and repair in V79 cells

“…The present investigation extends these studies, and describes the protective effects of WR-1065 on the radiation induced double-strand DNA breaks and repair using the neutral elution assay (Bradley & Kohn, 1979). This procedure is believed to correlate better with radiation induced cell killing (Hutchinson, 1978;Radford, 1985) but is relatively insensitive and requires extremely high, supra-lethal radiation doses. Recent reports (Tilby, 1984;Evans et al, 1986) have expressed concern that the pH originally suggested for the neutral elution procedure (pH 9.6) may include some single-stranded DNA.…”

“…In addition, these authors reported that the presence of the protector during repair inhibits strand rejoining in irradiated cells. Double-strand breaks (DSB) are widely believed to be more biologically relevant than SSB, and DSB have been implicated as the critical event in radiation-induced cell killing (Hutchinson, 1978;Radford, 1985;Ward, 1986). The neutral elution technique, developed by Bradley and Kohn (1979) measures DNA DSB.…”

SiDNA and Other Tools for the Indirect Induction of DNA Damage Responses

“…After these complex lesions, DSBs are the most harmful lesions to the cell (Ward, 1975). It has been shown, in rodent cells, that the extent of cell death is directly correlated with the yield of DSB under various X-ray irradiation conditions (Radford, 1985). IR is therefore often used in investigations of the cellular response to DSBs.…”

X-irradiation induces cell death in fetal fibroblasts

“…Improperly repaired DSB may result in DNA sequence integrity alterations or to cell death (6)(7)(8)(9)(10)(11). While excessive cell death may lead to embryonic malformations and growth retardation, persisting alterations in DNA may be transmitted to the daughter cells of the embryos thereby increasing the risk for postnatal cancer or genetic diseases.…”