Metabolism of low-dose inorganic arsenic in a central European population: influence of sex and genetic polymorphisms.
Anna-Lena Lindberg,Rajesh Kumar,Walter Goessler,Ranjit K. Thirumaran,Eugen Gurzau,Kvetoslava Koppova,Peter Rudnai,Giovanni Leonardi,Tony Fletcher,Marie Vahter +9 more
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TLDR
The results show that the M287T (T→C) polymorphism in the AS3MT gene, the A222V (C→T) polymorphisms in the MTHFR gene, body mass index, and sex are major factors that influence arsenic metabolism in this population, with a median of 8.0 μg/L arsenic in urine.Abstract:
BACKGROUND: There is a wide variation in susceptibility to health effects of arsenic, which, in part, may be due to differences in arsenic metabolism. Arsenic is metabolized by reduction and methylation reactions, catalyzed by reductases and methyltransferases. OBJECTIVES: Our goal in this study was to elucidate the influence of various demographic and genetic factors on the metabolism of arsenic. METHODS: We studied 415 individuals from Hungary, Romania, and Slovakia by measuring arsenic metabolites in urine using liquid chromatography with hydride generation and inductively coupled plasma mass spectrometry (HPLC-HG-ICPMS). We performed genotyping of arsenic (+III) methyltransferase (AS3MT), glutathione S-transferase omega 1 (GSTO1), and methylene-tetrahydrofolate reductase (MTHFR). RESULTS: The results show that the M287T (T-->C) polymorphism in the AS3MT gene, the A222V (C-->T) polymorphism in the MTHFR gene, body mass index, and sex are major factors that influence arsenic metabolism in this population, with a median of 8.0 microg/L arsenic in urine. Females C) polymorphism in the AS3MT gene on the methylation capacity was much more pronounced in men than in women. CONCLUSIONS: The factors investigated explained almost 20% of the variation seen in the metabolism of arsenic among men and only around 4% of the variation among women. The rest of the variation is probably explained by other methyltransferases backing up the methylation of arsenic.read more
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Arsenic Exposure and Toxicology: A Historical Perspective
TL;DR: The mode of action of arsenic for its disease endpoints is currently under study, and two key areas are the interaction of trivalent arsenicals with sulfur in proteins and the ability of arsenic to generate oxidative stress.
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Effects of arsenic on maternal and fetal health.
TL;DR: The fetus and infant are probably partly protected by the increased methylation of arsenic during pregnancy and lactation; the infant is also protected by low arsenic excretion in breast milk.
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A review on environmental factors regulating arsenic methylation in humans.
TL;DR: Methylation capacity might reduce with increasing dosage of arsenic exposure, women, especially at pregnancy, have better methylation capacity than their men counterparts, probably due to the effect of estrogen, and age shows inconsistent relevance in adults.
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Health effects of early life exposure to arsenic
TL;DR: An epidemiological study indicated that exposure to arsenic in drinking water during early childhood or in utero was associated with an increased mortality in young adults from both malignant and non-malignant lung disease and a series of experimental animal studies provide strong support for late effects of arsenic, including various forms of cancer, following intrauterine arsenic exposure.
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Gender and age differences in the metabolism of inorganic arsenic in a highly exposed population in Bangladesh
Anna Lena Lindberg,Eva Charlotte Ekström,Barbro Nermell,Mahfuzar Rahman,Bo Lönnerdal,Lars Åke Persson,Marie Vahter +6 more
TL;DR: Overall, exposure level of arsenic, gender and age explained at most 30% of the variation in the present study, indicating that genetic polymorphisms are the most important factor influencing the metabolism of inorganic arsenic.
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