It is well established that inorganic arsenic is causally associated with lung cancer via inhalation and skin cancer via ingestion. Epidemiological evidence based on studies in Taiwan suggests that ingestion of inorganic arsenic may also cause other more fatal internal cancers, with the highest relative risks reported for bladder cancer. Here, we have used a biological marker of response, the micronucleus assay in exfoliated bladder cells, to evaluate the possible genotoxic effects of chronic arsenic ingestion on the bladder. The overall objective of this study was to compare the frequency of micronucleated cells in exfoliated bladder and buccal cells between a group of 18 individuals in Nevada who chronically ingested high levels of inorganic arsenic from their well water (average level, 1,312 micrograms/liter) and an individually matched control group with low exposure to arsenic (average level, 16 micrograms/liter). A 1.8-fold increase (90% confidence interval, 1.06-2.99) was observed in the weighted mean frequency of micronucleated bladder cells in the exposed group (2.79 per 1000 cells) compared with the unexposed group (1.57 per 1000 cells). In addition, the frequency of micronucleated bladder cells was positively associated with the urinary concentration of inorganic arsenic plus its methylated metabolites (Spearman correlation = 0.33; P = 0.03). In contrast, there was no increase in micronucleated buccal cells associated with arsenic ingestion (frequency ratio = 1.0; 90% confidence interval, 0.65-1.53). The results of this study provide evidence that chronic ingestion of high levels of inorganic arsenic in drinking water is associated with an increased frequency of micronucleated bladder cells. These findings are consistent with a genotoxic effect of arsenic on bladder cells, but a larger study is needed to confirm them.

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