INCREASED MICRONUCLEI IN EXFOLIATED BLADDER CELLS OF INDIVIDUALS WHO CHRONICALLY INGEST ARSENIC-CONTAMINATED WATER IN NEVADA

It is well established that inorganic arsenic is causally associated w ith lung cancer via inhalation and skin cancer via ingestion. Epidemio logical evidence based on studies in Taiwan suggests that ingestion of inorganic arsenic may also cause other more fatal internal cancers, w ith the highest relative risks reported for bladder cancer. Here, we h ave used a biological marker of response, the micronucleus assay in ex foliated bladder cells, to evaluate the possible genotoxic effects of chronic arsenic ingestion on the bladder. The overall objective of thi s study was to compare the frequency of micronucleated cells in exfoli ated bladder and buccal cells between a group of 18 individuals in Nev ada who chronically ingested high levels of inorganic arsenic from the ir well water (average level, 1,312 mu g/liter) and an individually ma tched control group with low exposure to arsenic (average level, 16 mu g/liter). A 1.8-fold increase (90% confidence interval, 1.06-2.99) wa s observed in the weighted mean frequency of micronucleated bladder ce lls in the exposed group (2.79 per 1000 cells) compared with the unexp osed group (1.57 per 1000 cells). In addition, the frequency of micron ucleated bladder cells was positively associated with the urinary conc entration of inorganic arsenic plus its methylated metabolites (Spearm an correlation = 0.33; P = 0.03). In contrast, there was no increase i n micronucleated buccal cells associated with arsenic ingestion (frequ ency ratio = 1.0; 90% confidence interval, 0.65-1.53). The results of this study provide evidence that chronic ingestion of high levels of i norganic arsenic in drinking water is associated with an increased fre quency of micronucleated bladder cells. These findings are consistent with a genotoxic effect of arsenic on bladder cells, but a larger stud y is needed to confirm them.