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in Drinking Water May Inhibit DNA Repair
(ApriL 18, 2003) Exposure to small amounts of arsenic in drinking water may inhibit expression of genes involved in a critical 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 Dr. 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.
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 Dr. 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."
Although small amounts of arsenic occur naturally in some local sources of drinking water, environmentalists believe that chromated copper arsenate (CCA) pressure-treated wood will increase exposure, both directly and through leaching into soil and groundwater. Beyond Pesticides is currently suing the Environmental Protection Agency (EPA) to ban CCA and other heavy-duty wood preservatives.