A concise review of the toxicity and carcinogenicity of dimethylarsinic acid

Dimethylarsinic acid (DMA) has been used as a herbicide (cacodylic acid) an d is the major metabolite formed after exposure to tri- (arsenite) or penta valent (arsenate) inorganic arsenic (iAs) via ingestion or inhalation in bo th humans and rodents. Once viewed simply as a detoxification product of iA s, evidence has accumulated in recent years indicating that DMA itself has unique toxic properties. DMA induces an organ-specific lesion - single stra nd breaks in DNA - in the lungs of both mice and rats and in human lung cel ls in vitro. Mechanistic studies have suggested that this damage is due mai nly to the peroxyl radical of DMA and production of active oxygen species b y pulmonary tissues. Multi-organ initiation-promotion studies have demonstr ated that DMA acts as a promotor of urinary bladder, kidney, liver and thyr oid gland cancers in rats and as a promotor of lung tumors in mice. Lifetim e exposure to DMA in diet or drinking water also causes a dose-dependent in crease in urinary bladder tumors in rats, indicating that DMA is a complete carcinogen. These data collectively suggest that DMA plays a role in the c arcinogenesis of inorganic arsenic. Published by Elsevier Science Ireland L td.