Processing arsenic: genes have a say in how it's metabolized. (Science Selections).

Arsenic has become notorious as a contaminant in drinking water worldwide because long-term ingestion of its inorganic form causes cancer and skin lesions. Studies are showing that some people are more affected by arsenic than others, probably due to genetic differences in how their bodies process the chemical. Now researchers from the University of California at Berkeley School of Public Health evaluate for the first time the degree to which family members resemble each other in their arsenic methylation capacities [EHP 110:729-733].

Joyce S. Chung and colleagues analyzed the urinary arsenic concentrations of 44 members of 11 Chilean families. The families all drank from one water source in their desert town of Chiu Chiu. The arsenic concentrations in the water were 750-800 [micro]g/L, more than 70 times the new standard in the United States of 10 [micro]g/L

Arsenic is metabolized when enzymes in the body attach a methyl group to it. Inorganic arsenic is converted first to monomethylarsenate and then to dimethylarsinate. The relative concentration of each in the urine is known as the methylation pattern.

The researchers compared methylation patters among family members. Siblings had more similar patterns with each other than with their parents, and more similar patterns with their parents than with nonrelatives. For example, the correlations for one measurement of methylation were 0.72 between siblings and 0.18 for parents after adjusting for other factors that may affect methylation patterns, such as age, sex, micronutrient levels, and total urinary arsenic. Whether nutritional factors and gene--environment interactions affect methylation patterns remains unclear and requires further study, the team noted.

The fact that sibling and parent--child pairs had greater correlation than nonrelative pairs demonstrates that the variation in arsenic methylation probably has a genetic basis, something that researchers had expected but had not previously shown. Genetic polymorphisms have already explained differences in other methylation systems, such as those for metabolizing drugs.

Researchers once thought that methylation reduced the toxicity of arsenic. However, it is now believed that the methylated forms of arsenic may be more toxic than arsenic itself and may be more important in the development of cancer and skin lesions, the team wrote.

Understanding methylation patterns and whether arsenic poisoning is worse in certain families may eventually have clinical benefits. "If one person is identified with an arsenic-caused disease, other family members could be screened," says coauthor Allan H. Smith. "In the long term, it might be possible to identify people who would be particularly susceptible and then minimize any exposure."