Identification of biomarkers of arsenic exposure and metabolism in urine using SELDI technology.

Arsenic, a naturally occurring element, is a known human carcinogen. It is a known cause of lung cancer via inhalation and skin cancer via ingestion. Recently IARC classified arsenic in drinking water as a human carcinogen including lung and bladder cancer as outcomes. To obtain mechanistic insight into arsenic toxicity and to identify novel biomarkers of exposure and early biologic effect, we examined the impact of arsenic exposure on the human proteome in a study of individuals exposed to arsenic in their drinking water. All subjects participated in an earlier study of micronuclei in exfoliated bladder cells to evaluate the possible genotoxic effects of chronic arsenic ingestion on the bladder. The study was conducted in Churchill County, NV, in a location where private wells were sometimes contaminated with high concentrations of arsenic. Because arsenic is thought to cause genotoxic damage to the bladder, we used urine from exposed and unexposed individuals to identify biomarkers of arsenic exposure and early biologic effect using SELDI technology. Exposed individuals had well characterized exposures (N = 18; average well water As concentration 1312 ug/L ±359). They were matched by age, gender, and smoking status to low-exposed controls (N = 18; average well water As concentration 16 ug/L ±7). First morning urine voids were collected and stored at −80◦C until they were used to measure