Both the environment and genes are important for concentrations of cadmium and lead in blood.

Concentrations of cadmium and lead in blood (BCd and BPb, respectively) are traditionally used as biomarkers of environmental exposure. We estimated the influence of genetic factors on these markers in a cohort of 61 monozygotic and 103 dizygotic twin pairs (mean age = 68 years, range = 49-86). BCd and BPb were determined by graphite furnace atomic absorption spectrophotometry. Variations in both BCd and BPb were influenced by not only environmental but also genetic factors. Interestingly, the genetic influence was considerably greater for nonsmoking women (h(2) = 65% for BCd and 58% for BPb) than for nonsmoking men (13 and 0%, respectively). The shared familial environmental (c(2)) influence for BPb was 37% for men but only 3% for women. The association between BCd and BPb could be attributed entirely to environmental factors of mutual importance for levels of the two metals. Thus, blood metal concentrations in women reflect not only exposure, as previously believed, but to a considerable extent hereditary factors possibly related to uptake and storage. Further steps should focus on identification of these genetic factors and evaluation of whether women are more susceptible to exposure to toxic metals than men

Genetic Polymorphisms Influencing Arsenic Metabolism: Evidence from Argentina

The susceptibility to arsenic-induced diseases differs greatly between individuals, possibly due to interindividual variations in As metabolism that affect retention and distribution of toxic metabolites. To elucidate the role of genetic factors in As metabolism, we studied how polymorphisms in six genes affected the urinary metabolite pattern in a group of indigenous women (n = 147) in northern Argentina who were exposed to approximately 200 μg/L As in drinking water. These women had low urinary percentages of monomethylated As (MMA) and high percentages of dimethylated As (DMA). MMA has been associated with adverse health effects, and DMA has the lowest body retention of the metabolites. The genes studied were arsenic(+III)methyltransferase (AS3MT), glutathione S-transferase omega 1 (GSTO1), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), methylenetetrahydrofolate reductase (MTHFR), and glutathione S-transferases mu 1 (GSTM1) and theta 1 (GSTT1). We found three intronic polymorphisms in AS3MT (G12390C, C14215T, and G35991A) associated with a lower percentage of MMA (%MMA) and a higher percentage of DMA (%DMA) in urine. The variant homozygotes showed approximately half the %MMA compared with wild-type homozygotes. These polymorphisms were in strong linkage, with high allelic frequencies (72–76%) compared with other populations. We also saw minor effects of other polymorphisms in the multivariate regression analysis with effect modification for the deletion genotypes for GSTM1 (affecting %MMA) and GSTT1 (affecting %MMA and %DMA). For pregnant women, effect modification was seen for the folate-metabolizing genes MTR and MTHFR. In conclusion, these findings indicate that polymorphisms in AS3MT—and possibly GSTM1, GSTT1, MTR, and MTHFR—are responsible for a large part of the interindividual variation in As metabolism and susceptibility

Arsenic Metabolism by Human Gut Microbiota upon in Vitro Digestion of Contaminated Soils

BACKGROUND: Speciation analysis is essential when evaluating risks from arsenic (As) exposure. In an oral exposure scenario, the importance of presystemic metabolism by gut microorganisms has been evidenced with in vivo animal models and in vitro experiments with animal microbiota. However, it is unclear whether human microbiota display similar As metabolism, especially when present in a contaminated matrix. OBJECTIVES: We evaluated the metabolic potency of in vitro cultured human colon microbiota toward inorganic As (iAs) and As-contaminated soils. METHODS: A colon microbial community was cultured in a dynamic model of the human gut. These colon microbiota were incubated with iAs and with As-contaminated urban soils. We determined As speciation analysis using high-performance liquid chromatography coupled with inductively coupled plasma mass spectrometry. RESULTS: We found a high degree of methylation for colon digests both of iAs (10 mu g methylarsenical/g biomass/hr) and of As-contaminated soils (up to 28 mu g/g biomass/hr). Besides the formation of monomethylarsonic acid (MMA(V)), we detected the highly toxic monomethylarsonous acid (MMA(III)). Moreover, this is the first description of microbial thiolation leading to monomethylmonothioarsonic acid (MMMTA(V)). MMMTA(V), the toxicokinetic properties of which are not well known, was in many cases a major metabolite. CONCLUSIONS: Presystemic As metabolism is a significant process in the human body. Toxicokinetic studies aiming to completely elucidate the As metabolic pathway would therefore benefit from incorporating the metabolic potency of human gut microbiota. This will result in more accurate risk characterization associated with As exposures

Maternal Cadmium Exposure during Pregnancy and Size at Birth: A Prospective Cohort Study

Background: Cadmium (Cd) is an embryotoxic and teratogenic metal in a variety of animal species, but data from humans are limited

Breast-feeding Protects against Arsenic Exposure in Bangladeshi Infants

BACKGROUND: Chronic arsenic exposure causes a wide range of health effects, but little is known about critical windows of exposure. Arsenic readily crosses the placenta, but the few available data on postnatal exposure to arsenic via breast milk are not conclusive. AIM: Our goal was to assess the arsenic exposure through breast milk in Bangladeshi infants, living in an area with high prevalence of arsenic-rich tube-well water. METHODS: We analyzed metabolites of inorganic arsenic in breast milk and infant urine at 3 months of age and compared them with detailed information on breast-feeding practices and maternal arsenic exposure, as measured by concentrations in blood, urine, and saliva. RESULTS: Arsenic concentrations in breast-milk samples were low (median, 1 microg/kg; range, 0.25-19 microg/kg), despite high arsenic exposures via drinking water (10-1,100 microg/L in urine and 2-40 microg/L in red blood cells). Accordingly, the arsenic concentrations in urine of infants whose mothers reported exclusive breast-feeding were low (median, 1.1 microg/L; range, 0.3-29 microg/L), whereas concentrations for those whose mothers reported partial breast-feeding ranged from 0.4 to 1,520 microg/L (median 1.9 microg/L). The major part of arsenic in milk was inorganic. Still, the infants had a high fraction (median, 87%) of the dimethylated arsenic metabolite in urine. Arsenic in breast milk was associated with arsenic in maternal blood, urine, and saliva. CONCLUSION: Very little arsenic is excreted in breast milk, even in women with high exposure from drinking water. Thus, exclusive breast-feeding protects the infant from exposure to arsenic

Early-life nutritional and environmental determinants of thymic size in infants born in rural Bangladesh

The aim was to assess the impact of nutritional status and environmental exposures on infant thymic development in the rural Matlab region of Bangladesh. In a cohort of N-max 2094 infants born during a randomized study of combined interventions to improve maternal and infant health, thymic volume (thymic index, TI) was assessed by ultrasonography at birth and at 8, 24 and 52 weeks of age. Data on birth weight, infant anthropometry and feeding status were also collected. At all ages, TI was positively associated with infant weight and strongly associated with the month of measurement. Longer duration of exclusive breastfeeding resulted in a larger TI at 52 weeks. TI at birth and at 8 weeks correlated positively with birth weight, but by 24 and 52 weeks and when adjusted for infant weight this effect was no longer present. Thymic size was not affected by pre-natal maternal supplementation or by socioeconomic status but was correlated to arsenic exposure during pregnancy. In this population of rural Bangladeshi infants, thymic development is influenced by both nutritional and environmental exposures early in life. The long-term functional implications of these findings warrant further investigation

Nutritional Status Has Marginal Influence on the Metabolism of Inorganic Arsenic in Pregnant Bangladeshi Women

BACKGROUND: The interindividual variation in metabolism of inorganic arsenic (iAs), involving methylation via one-carbon metabolism, has been well documented, but the reasons remain unclear. OBJECTIVES: In this population-based study we aimed to elucidate the effect of nutrition on As methylation among women in Matlab, Bangladesh, where people are chronically exposed to iAs via drinking water. METHODS: We studied effects of macronutrient status using body mass index (BMI) among 442 women in early pregnancy (gestational week 8), and effects of micronutrient status (plasma folate, vitamin B12, zinc, ferritin, and selenium) among 753 women at gestational week 14. Arsenic metabolites in urine were measured by HPLC combined with hydride generation inductively coupled plasma mass spectrometry. RESULTS: The median concentration of As in urine was 97 microg/L (range, 5-1,216 microg/L, adjusted by specific gravity). The average proportions of iAs, monomethylarsonic acid, and dimethylarsinic acid in urine in gestational week 8 were 15%, 11%, and 74%, respectively. Thus, the women had efficient As methylation in spite of being poorly nourished (one-third had BMIs < 18.5 kg/m2) and having elevated As exposure, both of which are known to decrease As methylation. The metabolism of iAs was only marginally influenced by micronutrient status, probably because women, especially in pregnancy and with low folate intake, have an efficient betaine-mediated remethylation of homocysteine, which is essential for an efficient As methylation. CONCLUSIONS: In spite of the high As exposure and prevalent malnutrition, overall As methylation in women in early pregnancy was remarkably efficient. The As exposure level had the greatest impact on As methylation among the studied factors