Apr. 8, 2003 Hanover, NH – Exposure to small amounts of arsenic in drinking water may inhibit expression of genes involved in a critical housekeeping function that enables cells to repair damaged DNA, Dartmouth Medical School researchers find. The process, known as DNA repair, is considered a major biological defense in the body's ability to fight cancer.
The study, published in the April issue the International Journal of Cancer, is the first to report diminished expression of DNA repair genes in cells taken directly from humans exposed to arsenic through their environment, according to lead author, Dr. Angeline Andrew, research assistant professor of community and family medicine. She and colleagues Dr. Margaret Karagas, professor of community and family medicine, and Dr. Joshua Hamilton, associate professor of pharmacology and toxicology, compared the arsenic exposure of individuals to expression of DNA repair genes isolated from samples of the same person's blood.
"We were primarily interested in uncovering the mechanism to explain how arsenic causes cancer," said Andrew, noting that arsenic is a well established carcinogen. "This study supports the hypothesis that arsenic may act as a co-carcinogen --not directly causing cancer, but allowing other substances, such as cigarette smoke or ultraviolet light, to cause mutations in DNA more effectively."
The study sheds light on the environmental factors that can increase cancer risk among Americans. The researchers, all faculty in Dartmouth's Center for Environmental Health Sciences and the Norris Cotton Cancer Center, used molecular tools to expand an ongoing study analyzing cancer risk in people exposed to arsenic through their well water.
Previous studies by Karagas and colleagues had established that toenails provide a good biomarker for arsenic exposure -- that is, the arsenic levels in an individual's toenails are well correlated to that person's internal dose of arsenic. When they compared arsenic exposure of individuals, as determined by the toenail clippings, with expression of DNA repair genes isolated from samples of the same person's blood, the researchers found an association between arsenic exposure and expression of certain DNA repair genes.
In people with elevated arsenic exposure, several important DNA repair genes were expressed at lower levels than in unexposed controls. The affected genes are those involved in nucleotide excision repair -- one of the body's primary defenses against DNA damage caused by environmental agents. Normally, these genes code for proteins that unwind DNA, cut the damaged DNA parts out, seal the repaired DNA back together, and help determine which cells are irreparable and must die.
"It is often difficult to establish patterns in human studies, due to inter-individual variation," said Andrew, "but our findings are consistent with the hypothesis that inhibition of DNA repair capacity is a potential mechanism for the co-carcinogenic activity of arsenic." She points out that the study involved a small number of individuals and a larger study is needed to verify the results.
Though arsenic has been known as a poison since ancient times, people in many regions of the world consume small amounts of arsenic every day in their drinking water. Exposure to these relatively small doses of arsenic has been linked to several kinds of cancer. This study is the first in a series of projects to determine the mechanisms responsible for the link between cancer and arsenic.
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