Relative biological effectiveness of high linear energy transfer α-particles for the induction of DNA-double-strand breaks, chromosome aberrations and reproductive cell death in SW-1573 lung tumour cells

Abstract

Abstract. Ionizing radiation-induced foci (IRIF) of DNA repair-related proteins accumulated at DNA double-strand break (DSB) sites have been suggested to be a powerful biodosimetric tool. However, the relationship between IRIF induction and biologically relevant endpoints, such as cell death and formation of chromosome rearrangements is less clear, especially for high linear energy transfer (LET) radiation. It is thus not sufficiently established whether IRIF are valid indicators of biological effectiveness of the various radiation types. This question is more significant in light of the recent advancements in light ion-beam and radionuclide therapy. Dose-effect relationships were determined for the induction of DNA-DSBs, chromosome aberrations and reproductive cell death in cultured SW-1573 cells irradiated with γ-rays from a Cs-137 source or with α-particles from an Am-241 source. Values of relative biological effectiveness (RBE) of the high LET α-particles were derived for these effects. DNA-DSB were detected by scoring of γ-H2AX foci, chromosome aberrations by fragments and translocations using premature chromosome condensation and cell survival by colony formation. Analysis of dose-effect relations was based on the linear-quadratic model. Except for the survival curves, for other effects no significant contribution was derived of the quadratic term in the range of doses up to 2 Gy of γ-rays. Calculated RBE values derived for the linear component of dose-effect relations for γ-H2AX foci, cell reproductive death, chromosome fragments and colour junctions are 1.0±0.3, 14.7±5.1, 15.3±5.9 and 13.3±6.0, respectively. RBE values calculated at a certain biological effect level are 1, 4, 13 and 13, respectively. The RBE values derived from the LQ model are preferred as they are based on clinically relevant doses. The results show that with low LET radiation only a small fraction of the numerous DNA-DSBs yield chromosome damage and reproductive cell death. It is concluded that many of the chromosomal aberrations detected by premature chromosome condensation do not cause reproductive cell death. Furthermore, RBE values for DNA-DSB detectable by γ-H2AX foci shortly after irradiation, provide no information relevant to applications of high LET radiation in radiotherapy. The RBE values of chromosome aberrations assessed by premature chromosome condensation are close to the value for reproductive cell death. This suggests possible relevance to assess RBE values for radiotherapy with high LET ions.

Chronic exposure by ingestion of environmentally relevant doses of226Ra leads to transient growth perturbations in fathead minnow (Pimephales promelas, Rafinesque, 1820)

“…Chronic exposure is also more likely to be relevant. Th ere are considerable uncertainties concerning the relative biological eff ectiveness (RBE) of alpha versus gamma exposures with estimated RBE values ranging from 1 -50 (UNSCEAR 2008, table 16, and Wang 1963, Th omas et al 2003, Hofmann et al 2004, Chambers et al 2006, Priest and Hoel 2010, Franken et al 2012. Th e relationship between acute and chronic exposures is similarly uncertain.…”

Genomic Instability Induced by Ionizing Radiation in Human Hepatocytes

“…Ionizing radiation is known to induce cellular DNA damage manifested as chromosomal aberrations, gene mutations, and highfrequency gene rearrangement (Ameziane-ElHassani et al 2010;Franken et al 2012;Li et al 2007;Mondello et al 2011). These adverse effects may be due to direct exposure to irradiation and appear immediately after treatment.…”

Decay of γ-H2AX foci correlates with potentially lethal damage repair and P53 status in human colorectal carcinoma cells

“…Cells were grown on sterile cover slips (21 x 26 mm) placed in culture dishes [2,34]. The cells were reseeded at a density of 2.5 x 10 5 cells per cover slip.…”

“…In order to determine the number of γ-H2AX foci induced by ionizing radiation, the microscope slides were examined using a Leica DM RA HC fluorescence microscope equipped with a CCD camera under a 100x objective lens [9,34]. Fluorescent photomicrographs of γ-H2AX foci were obtained using custommade software.…”