Different contributions of the indirect effects of γ-rays on the cytotoxicity in M10 and XRCC4 transfected M10 cells

Abstract

The protective effects of dimethyl sulfoxide (DMSO) against cell killing by (137)Cs gamma-rays were investigated in XRCC4-deficient cell line M10, XRCC4-complemented M10 and the parental mouse leukemia cell line L5178Y. Cell survival was determined by the colony-forming ability. M10 cells were more sensitive to gamma-ray-induced cell death than L5178Y and complemented M10 cells. Cell survival was increased in both M10 and L5178Y in the presence of DMSO. However, estimation of the DMSO-protectable fraction revealed a smaller protectable fraction for M10 cells than for L5178Y cells, indicating that indirect effects contributed in a smaller extent to the cytotoxicity in M10 than that in L5178Y. This effect is due to XRCC4 deficiency, since transfection of XRCC4 cDNA into M10 cells restored the radioprotective effects of DMSO to the level seen in L5178Y. In M10 cells, the killing effects of high LET radiation (Auger electrons from (125)I-antipyrine, carbon ions with an LET of 166 keV microm(-1)) were similar to those of low LET radiation ((137)Cs gamma-rays, characteristic X-rays from (125)I-bovine serum albumin). We discuss that lethal lesions produced by indirect actions in L5178Y and XRCC4-complemented M10 cells may differ, at least in part, from DNA double-strand breaks repairable by non-homologous end joining.

OH Radicals from the Indirect Actions of X-Rays Induce Cell Lethality and Mediate the Majority of the Oxygen Enhancement Effect

“…Conversely, the lethal damage induced by the direct action of X rays are less affected by oxygen concentration. Ó 2013 by Radiation Research Society INTRODUCTION Over the past few years, we published studies on the role of free radicals in the biological response to heavy-ion radiation (1)(2)(3)(4)(5). It is well established, that X rays induce DNA damage by two interacting mechanisms: Indirect actions which are mediated by radicals arising from water radiolysis; and direct actions due to the deposition of radiation energy directly on DNA.…”