Hornhardt Sabine, Gomolka Maria, Walsh Linda, Jung Thomas
BfS-Federal Office for Radiation Protection, Department of Radiation Protection and Health, Ingolstädter Landstr. 1, 85764 Oberschleissheim, Germany.
Mutat Res. 2006 Aug 30;600(1-2):165-76. doi: 10.1016/j.mrfmmm.2006.04.002. Epub 2006 Jun 9.
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.
在辐射防护领域，辐射与其他有毒物质的联合暴露被视为一个重要的研究领域。为阐明同时暴露的基本机制，研究了致癌物及环境毒物镉与两种砷化合物（亚砷酸盐和三氧化二砷）在人淋巴母细胞（TK6）中与γ辐射的相互作用。γ辐射可诱导显著的遗传毒性效应，如微核形成、DNA损伤和细胞凋亡，而在无毒浓度下，砷和镉对这些细胞损伤指标无显著影响。然而，与γ辐射联合时，三氧化二砷诱导的凋亡率比单一效应之和更具叠加性。在此，与照射的对照细胞相比，凋亡细胞水平以剂量依赖方式增加，最高可达两倍。在任何测试的浓度或辐射剂量下，亚砷酸盐均未诱导出显著的叠加效应。另一方面，在诱导DNA-蛋白质交联方面，三氧化二砷的效果不如亚砷酸盐。这些数据表明，这两种砷化合物在细胞内通过不同途径相互作用。硫酸镉与亚砷酸盐一样，在低浓度与γ辐射联合时对细胞凋亡无显著影响，而在高浓度时甚至可降低辐射诱导的细胞凋亡。在1μM硫酸镉作用下，观察到对微核诱导有叠加效应，与照射的对照细胞相比增加高达80%。镉和三氧化二砷的毒性浓度似乎可降低微核诱导。此处呈现的结果表明，接近自然环境中浓度的相对低浓度的砷和镉可能会干扰辐射效应。已确定两种砷化合物在作用上存在差异。
