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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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Available from: Sabine Hornhardt, Feb 26, 2014
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    • "The multiple stressor effects of Cd and gamma rays on Wistar rats were studied through their enzyme activities, where a synergistic increase was reported (Salovsky et al 1993). Another study on human lymphoblastoid cells through the frequency of micronucleus formation showed an additive effect of Cd and gamma-ray exposure (Hornhardt et al 2006). An in vivo antagonistic effect was reported by Privezentsev et al (1996). "
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    ABSTRACT: An adaptive response is a biological response where the exposure of cells or animals to a low priming exposure induces mechanisms that protect the cells or animals against the detrimental effects of a subsequent larger challenging exposure. In realistic environmental situations, living organisms can be exposed to a mixture of stressors, and the resultant effects due to such exposures are referred to as multiple stressor effects. In the present work we demonstrated, via quantification of apoptosis in the embryos, that embryos of the zebrafish (Danio rerio) subjected to a priming exposure provided by one environmental stressor (cadmium in micromolar concentrations) could undergo an adaptive response against a subsequent challenging exposure provided by another environmental stressor (alpha particles). We concluded that zebrafish embryos treated with 1 to 10 μM Cd at 5 h postfertilisation (hpf) for both 1 and 5 h could undergo an adaptive response against subsequent ∼4.4 mGy alpha-particle irradiation at 10 hpf, which could be interpreted as an antagonistic multiple stressor effect between Cd and ionising radiation. The zebrafish has become a popular vertebrate model for studying the in vivo response to ionising radiation. As such, our results suggested that multiple stressor effects should be carefully considered for human radiation risk assessment since the risk may be perturbed by another environmental stressor such as a heavy metal.
    Journal of Radiological Protection 01/2013; 33(1):101-112. DOI:10.1088/0952-4746/33/1/101 · 1.32 Impact Factor
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    • "Additive, synergistic and antagonistic effects had been reported for Cd and gamma rays through in vitro and in vivo studies. Hornhardt et al. (2006) showed an additive effect of Cd and gamma ray exposure on human lymphoblastoid cells through the frequency of micronuclei formation. A synergistic effect between Cd and gamma ray on Wistar rats in terms of their enzyme activities were reported by Salovsky et al. (1993). "
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    ABSTRACT: The aim of this study was to demonstrate that zebrafish embryos subjected to a priming exposure provided by one environmental stressor (low-dose alpha particles) can induce an adaptive response against a subsequent challenging exposure provided by another environmental stressor (heavy metal Cd). The effect thus identified would be an antagonistic multiple stressor effect. The effects of alpha particle radiation and/or Cd on whole embryos were studied through quantification of apoptotic signals at 24 h post-fertilization (hpf). Embryos were stained with the vital dye acridine orange, followed by counting the stained cells. For each set of experiments, 30 dechorionated embryos were divided into three groups, each having ten embryos. The three groups of embryos were referred to as (A) the control group, which received no more further treatments after dechorionation, (B) Cd-treated group, which did not receive any priming exposure and would receive a challenging exposure at 10 hpf and (C) (alpha + Cd)-treated group, which would receive both priming and challenging exposures. We defined the normalized net number of apoptotic signals in the (alpha + Cd)-treated group as N (C) * = [(apoptotic signals for (alpha + Cd)-treated group - average apoptotic signals for the corresponding control group)/average apoptotic signals for the corresponding control group] and that in the Cd-treated group as N (B)* = [(apoptotic signals for Cd-treated group - average apoptotic signals for the corresponding control group)/ average apoptotic signals for the corresponding control group]. By using the non-parametric Mann-Whitney U statistic, we were able to show that N (C) * was significantly smaller than N (B) *(p = 0.006). These demonstrated an antagonistic multiple stressor effect between ionizing radiation and Cd through the induction of an adaptive response by the ionizing radiation against subsequent exposures to Cd.
    Environmental Science and Pollution Research 06/2012; 19(9):3831-9. DOI:10.1007/s11356-012-1032-8 · 2.76 Impact Factor
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    • "Although both compounds NaAsO 2 and As 2 O 3 possess arsenic in the trivalent form (As III ), some differences can exist between these compounds. Hornhardt et al. (2006) observed in a human lymphoblastoid cell line that, in association with radiation, NaAsO 2 was more effective in the induction of DNA protein cross-link than As 2 O 3 , while this last compound increased the levels of apoptotic cells. "
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    ABSTRACT: This study aimed to analyze antioxidant responses and oxidative damage induced by two inorganic forms of arsenic (As; As(III) and As(V)) in an estuarine polychaete species, Laeonereis acuta (Nereididae). The capacity of arsenic biotransformation was also evaluated through the methylation process considering the activity of a key enzyme involved in the metabolization process. Worms were exposed to 50 μg (As(III) or As(V))/l during 2 or 7 days, plus a control group. Endpoints analyzed included concentration of reactive oxygen species (ROS), activities of antioxidant enzymes such as glutathione reductase (GR), total glutathione-S-transferase (GST), and omega isoform (GST Ω), glucose-6-phosphate deshydrogenase (G6PDH), levels of the antioxidant glutathione (GSH), and lipid peroxides concentration (TBARS). Results showed: (1) GR inhibition after 2-day exposure to both As forms (p < 0.05); (2) GST Ω inhibition after 7-day exposure to As(III) paralleled by an increase in total GST activity (p < 0.05); (3) augmented G6PDH activity after 7-day exposure to both As forms (p < 0.05); (4) no differences in terms of ROS and TBARS; and (5) inhibition of GST Ω activity in As(III) exposed worms, which was concomitant with a lowering of mono- and dymethylated arsenic species. These results confirm the reactivity of some biochemical variables of L. acuta to As and indicates its importance as a sentinel species in estuarine regions with presence of arsenic.
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