Inorganic
arsenic (
arsenite and
arsenate) in
drinking water has been associated with
skin cancers in several countries such as Taiwan, Chile, Argentina, Bangladesh, and Mexico. This association has not been established in the United States. In addition, inorganic
arsenic alone in
drinking water does not cause
skin cancers in animals. We recently showed that concentrations as low as 1.25 mg/l
sodium arsenite were able to enhance the tumorigenicity of solar UV irradiation in mice. The
tumors were almost all
squamous cell carcinomas (SCCs). These data suggest that
arsenic in
drinking water may need a carcinogenic partner, such as sunlight, in the induction of
skin cancers.
Arsenite may enhance tumorigenicity via effects on DNA repair and DNA damage-induced cell cycle effects, leading to
genomic instability. Others have found that dimethlyarsinic
acid (DMA), a metabolite of
arsenite, can induce
bladder cancers at high concentrations in
drinking water. In those experiments,
skin cancers were not produced. Taken together, these data suggest that
arsenite (or possibly an earlier metabolite), and not DMA, is responsible for the
skin cancers, but a second genotoxic agent may be a requirement. The differences between the US and the other
arsenic-exposed populations with regard to
skin cancers might be explained by the lower levels of
arsenic in the US, less sun exposure, better nutrition, or perhaps
genetic susceptibility differences.