Comparative investigations of sodium arsenite, arsenic trioxide and cadmium sulphate in combination with gamma-radiation on apoptosis, micronuclei induction and DNA damage in a human lymphoblastoid cell line.

BfS-Federal Office for Radiation Protection, Department of Radiation Protection and Health, Ingolstädter Landstr. 1, 85764 Oberschleissheim, Germany.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis (Impact Factor: 4.44). 09/2006; 600(1-2):165-76. DOI: 10.1016/j.mrfmmm.2006.04.002
Source: PubMed

ABSTRACT In the field of radiation protection the combined exposure to radiation and other toxic agents is recognised as an important research area. To elucidate the basic mechanisms of simultaneous exposure, the interaction of the carcinogens and environmental toxicants cadmium and two arsenic compounds, arsenite and arsenic trioxide, in combination with gamma-radiation in human lymphoblastoid cells (TK6) were investigated. Gamma-radiation induced significant genotoxic effects such as micronuclei formation, DNA damage and apoptosis, whereas arsenic and cadmium had no significant effect on these indicators of cellular damage at non-toxic concentrations. However, in combination with gamma-radiation arsenic trioxide induced a more than additive apoptotic rate compared to the sum of the single effects. Here, the level of apoptotic cells was increased, in a dose-dependent way, up to two-fold compared to the irradiated control cells. Arsenite did not induce a significant additive effect at any of the concentrations or radiation doses tested. On the other hand, arsenic trioxide was less effective than arsenite in the induction of DNA protein cross-links. These data indicate that the two arsenic compounds interact through different pathways in the cell. Cadmium sulphate, like arsenite, had no significant effect on apoptosis in combination with gamma-radiation at low concentrations and, at high concentrations, even reduced the radiation-induced apoptosis. An additive effect on micronuclei induction was observed with 1muM cadmium sulphate with an increase of up to 80% compared to the irradiated control cells. Toxic concentrations of cadmium and arsenic trioxide seemed to reduce micronuclei induction. The results presented here indicate that relatively low concentrations of arsenic and cadmium, close to those occuring in nature, may interfere with radiation effects. Differences in action of the two arsenic compounds were identified.

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    ABSTRACT: The aim of this work was to investigate the impact of long-term exposure to low concentrations of sodium arsenite on the cellular response to ionising radiation. Human lymphoblastoid GM1899a cells were cultured in the presence of sodium arsenite for up to six months. Following chemical exposure, acute challenge doses of X-rays were given and chromosome damage (dicentrics, acentric fragments, translocations, micronuclei) as well as cell growth and changes in cell cycle kinetics were determined. Initial short-term chemical exposures determined 8ng/ml (60nM) sodium arsenite as a suitable concentration for chronic exposures, which is below the current World Health Organization limit for arsenic in drinking water. At this concentration, cell growth was slightly, but consistently, slower than in untreated cultures throughout the six-month exposure period. Long-term exposure to the chemical induced no dicentrics and did not significantly alter the yield of dicentrics induced by 1 Gy acute X-irradiation. Similar results were obtained for chromosome translocations. In contrast, exposure to 8ng/ml sodium arsenite induced significant levels of acentric fragments and micronuclei. Fragment/micronuclei data in combined treatment samples compared with single treatments were consistent with an additive effect of chemical and radiation exposure. As for X-rays, micronuclei induced by sodium arsenite tended to show no centromere in situ hybridisation signal, indicating that they represent structural aberrations rather than mis-segregated chromosomes. Similar results were obtained in human peripheral lymphocytes following short-term exposure to sodium arsenite or X-rays. Overall, an additive effect was observed for all combined exposures. Cellular radiation responses therefore seem to operate without any modulatory effects from chronic low level exposure to sodium arsenite in the systems analysed here.
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May 21, 2014