How arsenic acts: evidence of oxidative stress. (Science Selections).

Scientists have known that people chronically exposed to excessive levels of arsenic in drinking water can suffer skin sores, hypertension, and peripheral vascular disease, plus have a higher risk for certain cancers. Arsenic's mechanism of action in human illness has been unclear, but laboratory studies of cells and animals have shown that exposure to arsenic causes oxidative stress, a condition that damages cellular health and is a culprit in the development of many diseases. This month, a group of Chinese, Japanese, and U.S. scientists led by Jingbo Pi of the University of Tsukuba in Japan provide evidence that exposure to arsenic in drinking water results in oxidative stress in humans as well [EHP 110:331-336].

The team studied 43 residents in Wuyuan, Inner Mongolia, China. The study subjects, all members of the Han nationality, received their main arsenic exposure through groundwater, having drunk tube-well water for a mean duration of about 18 years.

The high-exposure group included 33 residents of Yindingtu and Shiba, two villages where tests of tube-well water showed that, at 0.41 mg/L, mean concentrations of inorganic arsenic were about 8.2 times higher than China's regulatory limit for drinking water and 41 times higher than the World Health Organization's guidelines for drinking water. These subjects showed various common symptoms of arsenic poisoning, including unusual loss or overgrowth of pigmentation, hyperkeratosis (a thickening of the outer skin), higher rates of peripheral vascular disorder, peripheral neuropathy, and liver swelling. The low-exposure comparison group included 10 residents from the village of Shahe, 35 miles away, who drank tube-well water with much lower arsenic concentrations (0.02 mg/L).

Two physicians questioned the subjects on their lifetime drinking water sources, health care history, diet, and use of alcohol and cigarettes. Two dermatologists, blinded with respect to arsenic exposure in the study participants, conducted physical examinations. Blood was drawn from the study participants, and serum was separated to measure lipid peroxide levels.

The team found that participants in the high-exposure group had significantly higher levels of lipid peroxide in serum--24.0% higher--compared to the low-exposure group. Lipid peroxide is a product of lipid oxidized by free radicals, chemicals that rapidly react with other chemicals, damaging cellular DNA and playing an important role in processes such as mutagenesis, carcinogenesis, and aging. An elevated lipid peroxide profile indicates oxidative stress.

Another indicator of oxidative stress in the high-exposure group was the subjects' nonprotein sulfhydryl (NPSH) mean concentration in whole blood. NPSH plays an important role in protecting against damage by free radicals--approximately 95% of NPSH is the antioxidant glutathione, which can scavenge free radicals, or bring about enzymatic and chemical changes that trap free radicals before they damage DNA and RNA. The high-exposure group showed mean blood NPSH concentrations that were 57.3% of those in the low-exposure group.

The authors suggest that NPSH depletion might have encouraged lipid peroxides to proliferate in the high-exposure group, or the subjects' NPSH might have become depleted because of overproduced free radicals caused by exposure to arsenic. While the precise mechanism needs further study, chronic exposure to arsenic in drinking water was clearly shown to induce oxidative stress.