Hypomethylation of inflammatory genes (COX2, EGR1, and SOCS3) and increased urinary 8-nitroguanine in arsenic-exposed newborns and children

Phookphan, Preeyaphan; Navasumrit, Panida; Waraprasit, Somchamai; Promvijit, Jeerawan; Chaisatra, Krittinee; Ngaotepprutaram, Thitirat; Ruchirawat, Mathuros

doi:10.1016/j.taap.2016.12.015

Cited by 32 publications

(25 citation statements)

References 69 publications

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“…In the current investigation, increased maternal arsenic exposure during pregnancy was also associated with increased levels of 8-nitroguanine in cord blood serum. These findings were in line with those from our recent study in a Thai cohort [20] that arsenic exposure in utero and continued exposure during childhood increased levels of urinary 8-nitroguanine in exposed newborns and in children through their early life. In addition, the levels of 8-nitroguanine was significantly correlated with promoter hypomethylation and increased expression of COX2 , EGR1 , and SOC3 , all of which are involved in inflammation.…”

Section: Discussionsupporting

confidence: 93%

“…A recent study in a Thai cohort showed that arsenic exposure in utero increased levels of urinary 8-nitroguanine in newborns which significantly correlated with increased expression of inflammatory genes ( COX2, EGR1 and SOCS3 ) in cord blood [20]. A follow-up study showed that these arsenic-exposed children had increased urinary 8-nitroguanine [20] and salivary 8-OHdG as well as decreased expression of human 8-oxoguanine DNA glycosylase 1 ( hOGG1 ), suggesting a defect in the repair of 8-OHdG [21]. These observations support the earlier findings in the same cohort that prenatal arsenic exposure increased expression of genes involved in various biological networks such as apoptosis, stress responses and inflammation [22].…”

Section: Introductionmentioning

confidence: 99%

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Exposure to arsenic in utero is associated with various types of DNA damage and micronuclei in newborns: a birth cohort study

et al. 2019

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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.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Exposure to arsenic in utero is associated with various types of DNA damage and micronuclei in newborns: a birth cohort study

et al. 2019

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“…The level of 8-nitroguanine was determined using a competitive enzyme immunoassay OxiSelect TM Nitrosative DNA/RNA Damage ELISA Kit (Cell Biolabs; STA-825), similar to Phookphan et al (2017) . For the analysis, 10 mg of the sample (total RNA or mRNA) was used.…”

Section: Methodsmentioning

confidence: 99%

RNA and mRNA Nitration as a Novel Metabolic Link in Potato Immune Response to Phytophthora infestans

et al. 2018

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Peroxynitrite (ONOO-) exhibits a well-documented nitration activity in relation to proteins and lipids; however, the interaction of ONOO- with nucleic acids remains unknown in plants. The study uncovers RNA and mRNA nitration as an integral event in plant metabolism intensified during immune response. Using potato-avr/vr Phytophthora infestans systems and immunoassays we documented that potato immunity is accompanied by two waves of boosted ONOO- formation affecting guanine nucleotides embedded in RNA/mRNA and protein tyrosine residues. The early ONOO- generation was orchestrated with an elevated level of protein nitration and a huge accumulation of 8-nitroguanine (8-NO2-G) in RNA and mRNA pools confirmed as a biomarker of nucleic acid nitration. Importantly, potato cells lacking ONOO- due to scavenger treatment and attacked by the avr pathogen exhibited a low level of 8-NO2-G in the mRNA pool correlated with reduced symptoms of programmed cell death (PCD). The second burst of ONOO- coincided both with an enhanced level of tyrosine-nitrated proteins identified as subtilisine-like proteases and diminished protease activity in cells surrounding the PCD zone. Nitration of both RNA/mRNA and proteins via NO/ONOO- may constitute a new metabolic switch in redox regulation of PCD, potentially limiting its range in potato immunity to avr P. infestans.

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“…In addition, arsenic influences gene expression by reprograming DNA methylation. In arsenic-exposed newborns and children, promoter hypomethylation and increased expression of three inflammatory genes was found [ 32 ]. Two other reports suggest that arsenic reduces whole DNA 5-methylcytosine methylation levels in the bladders [ 12 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

The interaction of arsenic and N-butyl-N-(4-hydroxybutyl)nitrosamine on urothelial carcinogenesis in mice

et al. 2017

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The bladder is an important organ for the storage of excreted water and metabolites. If metabolites with carcinogenic characteristics are present in urine, the urothelial lining of the bladder could be damaged and genetically altered. In this study, we analyzed the interaction of arsenic and N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) on mouse bladder carcinogenesis. Our previous study found that arsenic affects BBN-altered urothelial enzymatic activity, protein expression, DNA oxidation and global DNA CpG methylation levels. In this study, two mouse models were used. First, after administering a co-treatment of BBN and arsenic for 20 weeks, BBN alone led to a urothelial carcinoma formation of 20%, and arsenic promoted a BBN-induced urothelial carcinoma formation of 10%. The protein expression of GSTM1, GSTO1, NQO1, and p21 did not change by arsenic along with the BBN co-treatment, but the Sp1 expression increased. In the second mouse model, BBN was a pretreatment promoter; arsenic dose-dependently deteriorated BBN-promoted dysplasia by 10% and 40% at 10 ppm and 100 ppm, respectively. Conversely, BBN pretreatment also accelerated arsenic-induced dysplasia by 30%. The urothelial carcinogenic effect reversed after ceasing BBN for a period of 20 weeks. In summary, three conclusions were drawn from this study. The first is the mutual promotion of arsenic and BBN in bladder carcinogenesis. Second, arsenic dosages without bladder carcinogenicity (10 ppm) or with slight carcinogenicity (100 ppm) promote BBN-induced mice bladder cancer progression. Finally, the dysplastic urothelium had reverted to near-normal morphology after ceasing BBN intake for 20 weeks, providing a good suggestion for people who want to quit smoking.

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Hypomethylation of inflammatory genes (COX2, EGR1, and SOCS3) and increased urinary 8-nitroguanine in arsenic-exposed newborns and children

Cited by 32 publications

References 69 publications

Exposure to arsenic in utero is associated with various types of DNA damage and micronuclei in newborns: a birth cohort study

Exposure to arsenic in utero is associated with various types of DNA damage and micronuclei in newborns: a birth cohort study

RNA and mRNA Nitration as a Novel Metabolic Link in Potato Immune Response to Phytophthora infestans

The interaction of arsenic and N-butyl-N-(4-hydroxybutyl)nitrosamine on urothelial carcinogenesis in mice

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