Arsenic Exposure and its Association with Cancers among Residents with Wells in New Mexico's Border Counties - PROJECT SUMMARY. Inorganic arsenic is a known carcinogen and toxic chemical. Arsenic contamination in drinking water is an environmental public health concern in the United States (US) and worldwide. Almost 43 million, or 15%, of all US residents, depend on private or domestic wells as their exclusive source of drinking water. State and/or Federal agencies do not regulate domestic well water safety and quality. Instead, consumers are responsible for monitoring their water safety and quality. In New Mexico (NM), naturally occurring arsenic concentrations in drinking water are considered among the highest in the US. Of the 33 counties in NM, Doña Ana County, one of the border counties in NM, has the highest average arsenic concentration, exceeding the Environmental Protection Agency Maximum Contamination Level of 10 µg/L. This project will focus on rural, underserved counties along the NM-Mexico border, including Hidalgo, Doña Ana, Otero, Lea, Eddy, and Luna, with residents who have well in their households. The NM-Mexico six border counties reported an alarming incidence of 5,366 new age-adjusted arsenic-associated cancers per 100,000 population during the period 2016- 2020. Doña Ana County has the second-highest cancer incidence in NM. Rural people who live in NM-Mexico border counties are underprivileged with lower socioeconomic status and are unaware of arsenic toxicity on health. While the link between arsenic exposure and cancer burden is a nationwide issue, there is a simultaneous need to protect and prevent arsenic-related cancers due to the long latency period to develop cancer in rural, underprivileged people in southwestern border areas. A promising approach to examining links between arsenic contamination and cancer lies in urine biomarkers. In particular, 8-hydroxy-2'-deoxyguanosine (8-OHdG), F2- isoprostane, and 4-hydroxyneonal (4-HNE) lipid adducts are biomarkers for DNA damage and oxidative stress and can initiate cellular damage that leads in the carcinogenic pathway. Our collaborative research team of metal toxicity and carcinogen experts will detect metal-contaminated water and then identify the presence of biomarkers and arsenic in urine samples from 125 well-water-dependent adults in the six NM-Mexico border counties. Self-reported and doctor-diagnosed cancer history information provided by the participants will be used to track the cancer burden among arsenic-contaminated, well water users. This project will use the urinary arsenic, 8-OHdG, F2-isoprostane, and 4-HNE biomarkers to identify arsenic contamination; the presence of arsenic, DNA damage, oxidative stress, and cellular mutation; and arsenic-related cancer burdens in the rural underprivileged populations living on arsenic-contaminated well water in border counties at NM. This project will help students, including underrepresented groups in biomedical sciences, gain high-quality, hands-on research experiences in the execution, analysis, and reporting of a research study as guided by the PI. This project will significantly impact the PI, an early stage and new investigator, and allow to generate data to aid in more extensive federal grant proposals submitted in the future.