1. Toxicological properties of the thiolated inorganic arsenic and arsenosugar metabolite thio-dimethylarsinic acid in human bladder cells
- Author
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Aswin Mangerich, Till Weber, Sascha Beneke, Svenia Berndt, Franziska Ebert, Tanja Schwerdtle, Larissa Leffers, Alexander Bürkle, University of Zurich, and Schwerdtle, Tanja
- Subjects
1303 Biochemistry ,Metabolite ,Thio-dimethylarsinic acid ,Apoptosis ,Cell Cycle Proteins ,medicine.disease_cause ,Biochemistry ,Arsenicals ,chemistry.chemical_compound ,Cacodylic Acid ,DNA Breaks, Double-Stranded ,Arsenite ,Cell Death ,Cell Cycle ,Monosaccharides ,Caspase 2 ,Nuclear Proteins ,Recombinant Proteins ,Toxicity ,Molecular Medicine ,Arsenates ,Poly(ADP-ribose) Polymerases ,Programmed cell death ,Glycoside Hydrolases ,DNA damage ,Urinary Bladder ,Biological Availability ,Arsenic ,Cell Line ,Cellular bioavailability ,Inorganic Chemistry ,ddc:570 ,medicine ,Humans ,Sulfhydryl Compounds ,Poly(ADP-ribosyl)ation ,Carcinogen ,Adenosine Diphosphate Ribose ,1604 Inorganic Chemistry ,10079 Institute of Veterinary Pharmacology and Toxicology ,Hydrogen Peroxide ,NAD ,Bioavailability ,chemistry ,Gene Expression Regulation ,1313 Molecular Medicine ,570 Life sciences ,biology ,Genotoxicity ,DNA Damage - Abstract
Thio-dimethylarsinic acid (thio-DMA(V)) has recently been identified as human metabolite after exposure toward both the human carcinogen inorganic arsenic and arsenosugars, which are the major arsenical constituents of marine algae. This study aims to get further insight in the toxic modes of action of thio-DMA(V) in cultured human urothelial cells. Among others effects of thio-DMA(V) on eight cell death related endpoints, cell cycle distribution, genotoxicity, cellular bioavailability as well as for the first time its impact on DNA damage induced poly(ADP-ribosyl)ation were investigated and compared to effects induced by arsenite. The data indicate that thio-DMA(V) exerts its cellular toxicity in a similar or even lower concentration range, however most likely via different mechanisms, than arsenite. Most interestingly, thio-DMA(V) decreased damage-induced cellular poly(ADP-ribosyl)ation by 35,000-fold lower concentrations than arsenite. The inhibition of this essential DNA-damage induced and DNA-repair related signaling reaction might contribute to inorganic arsenic induced toxicity, at least in the bladder. Therefore, and also because thio-DMA(V) is to date by far the most toxic human metabolite identified after arsenosugar intake, thio-DMA(V) should contemporary be fully (also in vivo) toxicologically characterized, to assess risks to human health related to inorganic arsenic but especially arsenosugar dietary intake.
- Published
- 2013