Clustered DNA Damages Induced by X Rays in Human Cells

TLDR

DNA double‑strand breaks are key radiation lesions, and bistranded clustered damages—multiple oxidized bases or strand breaks within a few turns—are thought to be hard to repair and thus critical, yet it was unclear whether sparsely ionizing radiation could generate such clusters in mammalian cells. The study aimed to test whether X‑ray exposure can generate clustered DNA damages in human cells. X‑ray irradiation produced abasic, oxidized pyrimidine, and oxidized purine clusters in human cells, with non‑DSB clusters accounting for about 70 % of complex lesions and their relative abundance varying with DNA context.

Abstract

Sutherland, B. M., Bennett, P. V., Sutherland, J. C. and Laval, J. Clustered DNA Damages Induced by X Rays in Human Cells. Radiat. Res. 157, 611–616 (2002).Although DNA DSBs are known to be important in producing the damaging effects of ionizing radiation in cells, bistranded clustered DNA damages—two or more oxidized bases, abasic sites or strand breaks on opposing DNA strands within a few helical turns—are postulated to be difficult to repair and thus to be critical radiation-induced lesions. Gamma rays can induce clustered damages in DNA in solution, and high-energy iron ions produce DSBs and oxidized pyrimidine clusters in human cells, but it was not known whether sparsely ionizing radiation can produce clustered damages in mammalian cells. We show here that X rays induce abasic clusters, oxidized pyrimidine clusters, and oxidized purine clusters in DNA in human cells. Non-DSB clustered damages comprise about 70% of the complex lesions produced in cells. The relative levels of specific cluster classes depend on the environment of the DNA.