June 26, 2005 Children with a particular variation in the CYT19 gene metabolize arsenic differently than adults with the same genetic variant, according to a new research report. The findings have important implications for the safety of drinking water worldwide and the use of arsenic as a cancer drug.
Arsenic, a heavy metal found around the globe, including the potable water supplies in many parts of Arizona and the West, has long been known to cause diseases such as circulatory and neurological disorders and cancer, predominantly of the skin, lung and bladder. In the body, arsenic is converted into different compounds, some highly toxic, through a series of biochemical reactions. It finally leaves the body in the urine.
The new research raises the possibility that the risk of developing arsenic-related disease is not the same for everybody because an individual's genetic makeup determines how the toxic metal is metabolized.
"Finding genetic determinants of arsenic metabolism may one day enable us to identify a super-susceptible group of people, and conversely, people who may be relatively resistant to the effects of arsenic," said Walter T. Klimecki, who led the research team. Klimecki is a research assistant professor of medicine at The University of Arizona's Arizona Respiratory Center and member of UA's BIO5 Institute.
The study is published in the current edition of Environmental Health Perspectives. Co-authors on the article are: Maria Mercedes Meza of the Sonora Institute of Technology (Mexico), Lizhi Yu, Yelitza Y. Rodriguez, Mischa Guild and David Thompson of the UA Arizona Respiratory Center and A. Jay Gandolfi of the UA department of pharmacology and toxicology.
The research is part of The University of Arizona's Superfund Basic Research Program, which is funded by the National Institutes of Health's National Institute for Environmental Health Sciences. The study was also supported by the Sonora Institute of Technology, Mexico.
Studying the distribution of arsenic metabolites in the body is important because they have different toxic potencies, said Klimecki. "Since we know that people carry different versions of DNA sequence for any given gene, we ask, 'Do people with one sequence variant metabolize arsenic differently than people with another sequence variant?'"
Klimecki and his coworkers found that the answer is yes.
The team analyzed arsenic levels in urine samples from 135 individuals from the Yaqui Valley in Sonora, Mexico, who were exposed to drinking water containing arsenic. The study participants ranged from 7 to 79 years in age. The researchers then analyzed DNA samples from the same individuals for variations in three genes known to play roles in arsenic metabolism. When they matched the arsenic levels in the urine samples to the variations in the genes, the researchers saw that the distribution of arsenic metabolites was different in urine samples from people with a certain variation of the CYT19 gene.
At that point, Klimecki's team was in for an unexpected discovery. When the team split up the data into different age groups, it turned out that the association between the particular form of CYT19 and altered urinary arsenic metabolites could only be found in children. Adults carrying the same variant of CYT19 do not metabolize arsenic differently. "Apparently the genetic variation affects arsenic metabolism only during childhood," said Klimecki.
This result could be important for cancer medicine, as arsenic is used as a drug in leukemia therapy. Individual differences in the way arsenic is metabolized could influence the drug's efficiency. "It sounds obvious, but researchers often fall into the trap of assuming that children are just miniature adults," said Klimecki. "Our data really shout out the pitfall in that."
Reference: Developmentally Restricted Genetic Determinants of Human Arsenic Metabolism: Association between Urinary Methylated Arsenic and CYT19 Polymorphisms in Children. Maria Mercedes Meza et al., Environmental Health Perspectives, Vol. 113, No. 6, June 2005.
Walter Klimecki, 520-626-7470, email@example.com
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