Trivalent arsenicals induce lipid peroxidation, protein carbonylation, and oxidative DNA damage in human urothelial cells.
Drinking arsenic-contaminated water is associated with an increased risk of bladder cancer. Arsenate (iAs(V)), arsenite (iAs(III)), monomethylarsonous acid (MMA(III)), monomethylarsonic acid (MMA(V)), dimethylarsinous acid (DMA(III)), and dimethylarsinic acid (DMA(V)) have all been detected in the urine of people who drink arsenic-contaminated water. The aim of this research was to investigate which of these arsenicals are more hazardous to human urothelial cells. The results indicate that iAs(III), MMA(III), and DMA(III) were more potent in inducing cytotoxicity, lipid peroxidation, protein carbonylation, oxidative DNA damage, nitric oxide, superoxide, hydrogen peroxide, and cellular free iron than MMA(V), DMA(V), and iAs(V) in human urothelial carcinoma and transformed cells. However, the results did not show convincingly that the trivalent arsenicals were more potent than pentavalent arsenicals in decreasing the intracellular contents of total thiol, protein thiol, and reduced glutathione. Induction of oxidative DNA damage was observed with 0.2 microM of iAs(III), MMA(III), or DMA(III) as early as 1h. Because of its high oxidative damage, higher proportion in urine, and lower cytotoxicity, DMA(III) may be the most hazardous arsenical to human urothelial cells.
Wang
Tsing-Cheng
TC
Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 11529, Taiwan.
Jan
Kun-Yan
KY
Wang
Alexander S S
AS
Gurr
Jia-Ran
JR
D020261:Arsenic Poisoning / Q000235:genetics* / Q000378:metabolism*; D001152:Arsenicals / Q000737:chemistry*; D002101:Cacodylic Acid / Q000031:analogs & derivatives / Q000633:toxicity; D002460:Cell Line; D004249:DNA Damage; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D010084:Oxidation-Reduction; D050050:Protein Carbonylation / Q000187:drug effects*; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced; D019459:Urothelium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D014874:Water Pollutants, Chemical / Q000633:toxicity
D001152:Arsenicals; D014874:Water Pollutants, Chemical; C472511:dimethylarsinous acid; D002101:Cacodylic Acid; D005978:Glutathione