Andrewes Paul, Kitchin Kirk T, Wallace Kathleen
Environmental Carcinogenesis Division, Office of Research and Development, National Heath and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27709, USA.
Toxicol Appl Pharmacol. 2004 Jan 1;194(1):41-8. doi: 10.1016/j.taap.2003.08.012.
Antimony is classified as "possibly carcinogenic to humans" and there is also sufficient evidence for antimony carcinogenicity in experimental animals. Stibine is a volatile inorganic antimony compound to which humans can be exposed in occupational settings (e.g., lead-acid battery charging). Because it is highly toxic, stibine is considered a significant health risk; however, its genotoxicity has received little attention. For the work reported here, stibine was generated by sodium borohydride reduction of potassium antimony tartrate. Trimethylstibine is a volatile organometallic antimony compound found commonly in landfill and sewage fermentation gases at concentrations ranging between 0.1 and 100 microg/m3. Trimethylstibine is generally considered to pose little environmental or health risk. In the work reported here, trimethylstibine was generated by reduction of trimethylantimony dichloride using either sodium borohydride or the thiol compounds, dithioerythritol (DTE), L-cysteine, and glutathione. Here we report the evaluation of the in vitro genotoxicities of five antimony compounds-potassium antimony tartrate, stibine, potassium hexahydroxyantimonate, trimethylantimony dichloride, and trimethylstibine-using a plasmid DNA-nicking assay. Of these five antimony compounds, only stibine and trimethylstibine were genotoxic (significant nicking to pBR 322 plasmid DNA). We found stibine and trimethylstibine to be about equipotent with trimethylarsine using this plasmid DNA-nicking assay. Reaction of trimethylantimony dichloride with either glutathione or L-cysteine to produce DNA-damaging trimethylstibine was observed with a trimethylantimony dichloride concentration as low as 50 microM and L-cysteine or glutathione concentrations as low as 500 and 200 microM, respectively, for a 24 h incubation.
锑被归类为“可能对人类致癌”，并且在实验动物中也有足够的证据证明锑具有致癌性。锑化氢是一种挥发性无机锑化合物，人类在职业环境（如铅酸电池充电）中可能会接触到。由于其毒性极高，锑化氢被认为是重大的健康风险；然而，其遗传毒性却很少受到关注。在本文报道的研究中，锑化氢是通过硼氢化钠还原酒石酸锑钾生成的。三甲基锑是一种挥发性有机金属锑化合物，常见于垃圾填埋场和污水发酵气体中，浓度范围在0.1至100微克/立方米之间。一般认为三甲基锑对环境或健康的风险很小。在本文报道的研究中，三甲基锑是通过用硼氢化钠或硫醇化合物二硫苏糖醇（DTE）、L-半胱氨酸和谷胱甘肽还原二氯化三甲基锑生成的。在此，我们报告了使用质粒DNA切口试验对五种锑化合物——酒石酸锑钾、锑化氢、六羟基锑酸钾、二氯化三甲基锑和三甲基锑——的体外遗传毒性进行的评估。在这五种锑化合物中，只有锑化氢和三甲基锑具有遗传毒性（对pBR 322质粒DNA有明显切口）。我们发现，使用这种质粒DNA切口试验，锑化氢和三甲基锑与三甲基胂的毒性大致相当。在24小时的孵育中，观察到二氯化三甲基锑与谷胱甘肽或L-半胱氨酸反应生成具有DNA损伤作用的三甲基锑，二氯化三甲基锑的浓度低至50微摩尔，L-半胱氨酸或谷胱甘肽的浓度分别低至500和200微摩尔。
