Plasmid DNA damage caused by stibine and trimethylstibine

• Published in: Toxicology and applied pharmacology 2004, Vol.194 (1), p.41-48
• Main Authors: Andrewes, Paul, Kitchin, Kirk T, Wallace, Kathleen
• Format: Article
• Language: English
• Subjects: Antimony; Antimony - toxicity; Biological and medical sciences; dithioerythritol; DNA Damage; DNA nicking; Genotoxicity; Glutathione; l-Cysteine; Medical sciences; Mutagens - toxicity; Organometallic Compounds - toxicity; Plasmids - drug effects; Plasmids - genetics; potassium hexahydroxyantimonate; Reactive oxygen species; sodium borohydride; Stibine; Toxicology; Trimethylantimony dichloride; Trimethylarsine; Trimethylstibine
• ISSN: 0041-008X; 1096-0333
• 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 μg/m 3. 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 μM and l-cysteine or glutathione concentrations as low as 500 and 200 μM, respectively, for a 24 h incubation.