Association between polymorphisms in arsenic metabolism genes and urinary arsenic methylation profiles in girls and boys chronically exposed to arsenic.

Disease manifestations or susceptibilities often differ among individuals exposed to the same concentrations of arsenic (As). These differences have been associated with several factors including As metabolism, sex, age, genetic variants, nutritional status, smoking, and others. This study evaluated the associations between four As metabolism-related gene polymorphisms/null genotypes with urinary As methylation profiles in girls and boys chronically exposed to As. In a total of 332 children aged 6-12 years, the frequency of AS3MT, GSTO1, GSTT1, and GSTM1 polymorphisms/null genotypes and As urinary metabolites were measured. The results revealed that total As and monomethyl metabolites of As (MMA) levels were higher in boys than in girls. No differences in the frequency of the evaluated polymorphisms were found between girls and boys. In AS3MT-Met287Thr carriers, %MMA levels were higher and second methylation levels (defined as dimethylarsinic acid divided by MMA) were lower. In children with the GSTM1 null genotype, second methylation levels were higher. In boys, a positive association between the AS3MT-Met287Thr polymorphism with %MMA and between the GSTO1-Glu155del and As(v) was found; whereas, a negative relationship was identified between AS3MT-Met287Thr and second methylation profiles. In girls, a positive association was found between the GSTO1-Ala140Asp polymorphism with second methylation levels. In conclusion, our data indicate that gender, high As exposure levels, and polymorphisms in the evaluated genes negatively influenced As metabolism. Environ. Mol. Mutagen. 57:516-525, 2016. © 2016 Wiley Periodicals, Inc.

Environmental arsenic exposure and sputum metalloproteinase concentrations.

Exposure to arsenic in drinking water is associated with an increased rate of lung cancer. The objective of this study was to determine whether arsenic exposure at relatively low concentrations (approximately 20 microg/L) is associated with changes in biomarkers of lung inflammation, as measured by the ratio of sputum metalloproteinase and antiproteinase activity. A total of 73 subjects residing in Ajo and Tucson, Arizona were recruited for this cross-sectional study. Tap water and first morning void urine were analyzed for arsenic. Matrix metalloproteinase 2 (MMP-2), 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) were measured in induced sputum. Household tap water arsenic levels in Ajo (20.3+/-3.7 microg/L) were higher than in those Tucson (4.0+/-2.3 microg/L), as were mean urinary total inorganic arsenic levels (29.1+/-20.4 and 11.0+/-12.0 microg/L, respectively). Log-normalized MMP-2, MMP-9, and TIMP-1 concentrations in sputum were not significantly different between towns. However, after adjusting for town, asthma, diabetes, urinary monomethylarsonic acid/inorganic arsenic, and smoking history, total urinary arsenic was negatively associated with MMP-2 and TIMP-1 levels in sputum and positively associated with the ratio of MMP-2/TIMP-1 and MMP-9/TIMP-1 in sputum. Increased sputum proteinase/antiproteinase activity suggests a potential toxic mechanism for low-level arsenic exposure.