TY - JOUR
T1 - Variability in human metabolism of arsenic
AU - Loffredo, Christopher A.
AU - Aposhian, H. Vasken
AU - Cebrian, Mariano E.
AU - Yamauchi, Hiroshi
AU - Silbergeld, Ellen K.
N1 - Funding Information:
Research by these investigators was supported by grants from NIEHS (HVA), from NIH-Fogarty and Conacyt-Mexico (MEC), and from the Heinz Family Foundation (EKS).
PY - 2003/6
Y1 - 2003/6
N2 - Estimating the nature and extent of human cancer risks due to arsenic (As) in drinking water is currently of great concern, since millions of persons worldwide are exposed to arsenic, primarily through natural enrichment of drinking water drawn from deep wells. Humans metabolize and eliminate As through oxidative methylation and subsequent urinary excretion. While there is debate as to the role of methylation in activation/detoxification, variations in arsenic metabolism may affect individual risks of toxicity and carcinogenesis. Using data from three populations, from Mexico, China, and Chile, we have analyzed the distribution in urine of total arsenic and arsenic species (inorganic arsenic (InAs), monomethyl arsenic (MMA), and dimethyl arsenic (DMA). Data were analyzed in terms of the concentration of each species and by evaluating MMA:DMA and (MMA+DMA):InAs ratios. In all persons most urinary As was present as DMA. Male:female differences were discernible in both high- and low-exposure groups from all three populations, but the gender differences varied by populations. The data also indicated bimodal distributions in the ratios of DMA to InAs and to MMA. While the gene or genes responsible for arsenic methylation are still unknown, the results of our studies among the ethnic groups in this study are consistent with the presence of functional genetic polymorphisms in arsenic methylation leading to measurable differences in toxicity. This analysis highlights the need for continuing research on the health effects of As in humans using molecular epidemiologic methods.
AB - Estimating the nature and extent of human cancer risks due to arsenic (As) in drinking water is currently of great concern, since millions of persons worldwide are exposed to arsenic, primarily through natural enrichment of drinking water drawn from deep wells. Humans metabolize and eliminate As through oxidative methylation and subsequent urinary excretion. While there is debate as to the role of methylation in activation/detoxification, variations in arsenic metabolism may affect individual risks of toxicity and carcinogenesis. Using data from three populations, from Mexico, China, and Chile, we have analyzed the distribution in urine of total arsenic and arsenic species (inorganic arsenic (InAs), monomethyl arsenic (MMA), and dimethyl arsenic (DMA). Data were analyzed in terms of the concentration of each species and by evaluating MMA:DMA and (MMA+DMA):InAs ratios. In all persons most urinary As was present as DMA. Male:female differences were discernible in both high- and low-exposure groups from all three populations, but the gender differences varied by populations. The data also indicated bimodal distributions in the ratios of DMA to InAs and to MMA. While the gene or genes responsible for arsenic methylation are still unknown, the results of our studies among the ethnic groups in this study are consistent with the presence of functional genetic polymorphisms in arsenic methylation leading to measurable differences in toxicity. This analysis highlights the need for continuing research on the health effects of As in humans using molecular epidemiologic methods.
KW - Arsenic
KW - Cancer
KW - Drinking water
KW - Genetic polymorphisms
KW - Methylation
UR - http://www.scopus.com/inward/record.url?scp=0038042653&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0038042653&partnerID=8YFLogxK
U2 - 10.1016/S0013-9351(02)00081-6
DO - 10.1016/S0013-9351(02)00081-6
M3 - Article
C2 - 12854687
AN - SCOPUS:0038042653
SN - 0013-9351
VL - 92
SP - 85
EP - 91
JO - Environmental research
JF - Environmental research
IS - 2
ER -