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EFFECTS OF INGESTED ARSENIC ON DNA AND CHROMOSOME IN HUMAN EXFOLIATED EPITHELIA
Citation:
Mumford, J. L. EFFECTS OF INGESTED ARSENIC ON DNA AND CHROMOSOME IN HUMAN EXFOLIATED EPITHELIA. Presented at Exfoliated Cells, Bioactive Food Components and Cancer Prevension Workshop, Bethesda, MD, May 23, 2003.
Description:
Effects of Ingested Arsenic on DNA and Chromosome in Human Exfoliated Epithelia
Judy L. Mumford, Human Studies Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711
Arsenic exposure has been associated with cancer in skin, bladder and lung. A new arsenic standard (10 g/L), in drinking water has been adopted by EPA in 2001. There are still great uncertainties on the mechanisms of arsenic carcinogenesis and cancer risk of arsenic at low doses in humans. Biomarkers useful for assessing health effects of arsenic at low dose is needed. The residents of Ba Men in Inner Mongolia have been exposed to a wide range of arsenic concentrations via drinking water and showed health effects. This provides us a good opportunity to assess the health effects of arsenic and evaluate the biomarkers in humans. Human exfoliated epithelial cells are non-invasive to collect and are appropriate for human epidemiological studies. Initially, a pilot study was conducted in Ba Men to determine if we can use human exfoliated cells to assess DNA and chromosomal damage from chronic arsenic exposure. The study included 19 high As-exposed individuals with hyperkeratosis and/or hyperpigmentation and 13 low or no exposure individuals. Drinking water samples were collected and analyzed for arsenic. The exfoliated epithelia, including buccal, sputum and urothelial cells, were collected from each subject and assayed for micronucleus frequency. DNA fragmentation in buccal cells were determined using DNA ladder and TUNEL assays. The results indicate that high levels of arsenic exposure induced elevated levels of micronuclei in all three cell types; higher levels of micronuclei were observed in buccal and sputum cells than urothelial cells. Subsequently, we conducted a larger study in Ba Men to determine if these biomarkers can be useful in assessing health effects at lower doses. A total of 321 Ba Men residents, exposed to low (<21 mg/L), medium (100-300 mg/L), or high (450-690 mg/L) concentrations of arsenic were included in the study. A subset (30 subjects from each dose group) of nonsmoking subjects' buccal cells were analyzed for micronuclei and DNA fragmentation. Results showed that increased micronucleus frequency and DNA fragmentation in buccal cells were associated with arsenic concentrations in water. Elevated micronucleus frequency were observed in the subjects exposed to medium and high doses whereas increase in DNA fragmentation was only observed in the high dose group. This study elucidated that chronic exposure to arsenic increased risk for chromosome and DNA damage. Studies in micronucleus and DNA fragmentation in human exfoliated epithelia are useful in assessing genotoxicity of arsenic and may potentially be useful in assessing cancer risk from chronic exposure to arsenic. (This abstract does not necessarily reflect EPA policy.)
References:
1. Feng, Z., Y. Xia, D. Tian, K. Wu, M. Schmitt, R. Kwok and J.L. Mumford (2001) DNA Damage in buccal epithelial cells from individuals chronically exposed to arsenic via drinking water in Inner Mongolia, China, Anticancer Research 21, 51-58.
2. Tian, D., H. Ma, Z. Feng, Y. Xia, X. C. Le, Z. Ni, J. Allen, B. Collins, D. Schreinemachers and J.L. Mumford (2001) Analyses of micronuclei in exfoliated epithelial cells from individuals chronically exposed to arsenic via drinking water in Inner Mongolia, China, J. Toxicology and Environmental Health 64, 473-484.