BackgroundAccumulating evidence indicates that in utero exposure to arsenic is associated with congenital defects and long-term disease consequences including cancers. Recent studies suggest that arsenic carcinogenesis results from epigenetic changes, particularly in DNA methylation. This study aimed to investigate DNA methylation changes as a result of arsenic exposure in utero and in vitro.MethodsFor the exposure in utero study, a total of seventy-one newborns (fifty-five arsenic-exposed and sixteen unexposed newborns) were recruited. Arsenic concentrations in the drinking water were measured, and exposure in newborns was assessed by measurement of arsenic concentrations in cord blood, nails and hair by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). In the in vitro study, human lymphoblasts were treated with arsenite at 0-100 μM for two, four and eight hours (short-term) and at 0, 0.5 and 1.0 μM for eight-weeks period (long-term). DNA methylation was analyzed in cord blood lymphocytes and lymphoblasts treated with arsenite in vitro. Global DNA methylation was determined as LINE-1 methylation using combined bisulfite restriction analysis (COBRA) and total 5-methyldeoxycytidine (5MedC) content which was determined by HPLC-MS/MS. Methylation of p53 was determined at the promoter region using methylation-specific restriction endonuclease digestion with MspI and HpaII.ResultsResults showed that arsenic-exposed newborns had significantly higher levels of arsenic in cord blood, fingernails, toenails and hair than those of the unexposed subjects and a slight increase in promoter methylation of p53 in cord blood lymphocytes which significantly correlated with arsenic accumulation in nails (p < 0.05) was observed, while LINE-1 methylation was unchanged. Short-term in vitro arsenite treatment in lymphoblastoid cells clearly demonstrated a significant global hypomethylation, determined as reduction in LINE-1 methylation and total 5-MedC content, and p53 hypermethylation (p < 0.05). However, a slight LINE-1 hypomethylation and transient p53 promoter hypermethylation were observed following long-term in vitro treatment.ConclusionsThis study provides an important finding that in utero arsenic exposure affects DNA methylation, particularly at the p53 promoter region, which may be linked to the mechanism of arsenic carcinogenesis and the observed increased incidence of cancer later in life.

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Background Growing evidence indicates that in utero arsenic exposures in humans may increase the risk of adverse health effects and development of diseases later in life. This study aimed to evaluate potential health risks of in utero arsenic exposure on genetic damage in newborns in relation to maternal arsenic exposure. Methods A total of 205 pregnant women residing in arsenic-contaminated areas in Hanam province, Vietnam, were recruited. Prenatal arsenic exposure was determined by arsenic concentration in mother’s toenails and urine during pregnancy and in umbilical cord blood collected at delivery. Genetic damage in newborns was assessed by various biomarkers of early genetic effects including oxidative/nitrative DNA damage (8-hydroxydeoxyguanosine, 8-OHdG, and 8-nitroguanine), DNA strand breaks and micronuclei (MN) in cord blood. Results Maternal arsenic exposure, measured by arsenic levels in toenails and urine, was significantly increased ( p <  0.05) in subjects residing in areas with high levels of arsenic contamination in drinking water. Cord blood arsenic level was significantly increased in accordance with maternal arsenic exposure ( p <  0.001). Arsenic exposure in utero is associated with genotoxic effects in newborns indicated as increased levels of 8-OHdG, 8-nitroguanine, DNA strand breaks and MN frequency in cord blood with increasing levels of maternal arsenic exposure. Maternal toenail arsenic level was significantly associated with all biomarkers of early genetic effects, while cord blood arsenic levels associated with DNA strand breaks and MN frequency. Conclusions In utero arsenic exposure is associated with various types of genetic damage in newborns potentially contributing to the development of diseases, including cancer, later in life.

Inhalable particulate matter (PM) is a health concern, and people living in large cities such as Bangkok are exposed to high concentrations. This exposure has been linked to respiratory and cardiac diseases and cancers of the lung and brain. Throughout 2018, PM was measured in northern Bangkok near a toll road (13.87°N, 100.58°E) covering all three seasons (cool, hot and rainy). PM10 was measured in 24- and 72-h samples. On selected dates aerodynamic size and mass distribution were measured as 3-day samples from a fixed 5th floor inlet. Particle number concentration was measured from the 5th floor inlet and in roadside survey measurements. There was a large fraction of particle number concentration in the sub-micron range, which showed the greatest variability compared with larger fractions. Metals associated with combustion sources were most found on the smaller size fraction of particles, which may have implications for associated adverse health outcomes because of the likely location of aerosol deposition in the distal airways of the lung. PM10 samples varied between 30 and 100 μg m−3, with highest concentrations in the cool season. The largest metal fractions present in the PM10 measurements were calcium, iron and magnesium during the hot season with average airborne concentrations of 13.2, 3.6 and 2.0 μg m−3, respectively. Copper, zinc, arsenic, selenium, molybdenum, cadmium, antimony and lead had large non-crustal sources. Principal component analysis (PCA) identified likely sources of the metals as crustal minerals, tailpipe exhaust and non-combustion traffic. A health risk analysis showed a higher risk of both carcinogenic and non-carcinogenic health effects in the drier seasons than the wet season due to ingestion of nickel, arsenic, cadmium and lead. Graphical abstract