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Exposure to brominated trihalomethanes in water during pregnancy and micronuclei frequency in maternal and cord blood lymphocytes.

ABSTRACT: BACKGROUND: Water disinfection by-products have been associated with an increased cancer risk. Micronuclei (MN) frequency in lymphocytes is a marker of genomic damage and can predict adult cancer risk. OBJECTIVE: We evaluated maternal exposure to drinking water brominated trihalomethanes (BTHM) in relation to MN frequency in maternal and cord blood lymphocytes. METHODS: MN frequency was examined in 214 mothers and 223 newborns from the Rhea mother-child cohort in Crete, Greece, in 2007-2008. Residential BTHM water concentrations were estimated during pregnancy using tap water analyses and modeling. Questionnaires on water related habits were used to estimate BTHM exposure from all routes. Associations between BTHM and MN frequency were estimated using negative binomial regression. RESULTS: BTHM concentrations in residential tap water during pregnancy ranged from 0.06 to 7.1 ?g/L. MN frequency in maternal binucleated lymphocytes was found to increase with BTHM concentrations in residential water for exposure during the first [rate ratio (RR) for 1 ?g/L=1.05; 95% CI: 1.00, 1.11] and second trimesters (RR for 1 ?g/L=1.03; 95% CI: 1.00, 1.06), and through all routes of BTHM exposure during the first trimester (RR for 1 ?g/week=3.14; 95% CI: 1.16, 8.50). CONCLUSIONS: These findings suggest that exposure to BTHM may increase the frequency of MN in maternal binucleated lymphocytes.

SUBMITTER: Stayner LT

PROVIDER: S-EPMC3888564 | biostudies-other | 2014 Jan

REPOSITORIES: biostudies-other

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Exposure to brominated trihalomethanes in water during pregnancy and micronuclei frequency in maternal and cord blood lymphocytes.

Stayner Leslie Thomas LT Pedersen Marie M Patelarou Evridiki E Decordier Ilse I Vande Loock Kim K Chatzi Leda L Espinosa Ana A Fthenou Eleni E Nieuwenhuijsen Mark J MJ Gracia-Lavedan Esther E Stephanou Euripides G EG Kirsch-Volders Micheline M Kogevinas Manolis M

Environmental health perspectives 20131101 1

<h4>Background</h4>Water disinfection by-products have been associated with an increased cancer risk. Micronuclei (MN) frequency in lymphocytes is a marker of genomic damage and can predict adult cancer risk.<h4>Objective</h4>We evaluated maternal exposure to drinking water brominated trihalomethanes (BTHM) in relation to MN frequency in maternal and cord blood lymphocytes.<h4>Methods</h4>MN frequency was examined in 214 mothers and 223 newborns from the Rhea mother-child cohort in Crete, Greece ...[more]

PMID: 24184846

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Project description:BACKGROUND: Leukemia incidence has increased in recent decades among European children, suggesting that early-life environmental exposures play an important role in disease development. OBJECTIVES: We investigated the hypothesis that childhood susceptibility may increase as a result of in utero exposure to carcinogens and hormonally acting factors. Using cord blood samples from the NewGeneris cohort, we examined associations between a range of biomarkers of carcinogen exposure and hormonally acting factors with micronuclei (MN) frequency as a proxy measure of cancer risk. Associations with gene expression and genotype were also explored. METHODS: DNA and protein adducts, gene expression profiles, circulating hormonally acting factors, and GWAS (genome-wide association study) data were investigated in relation to genomic damage measured by MN frequency in lymphocytes from 623 newborns enrolled between 2006 and 2010 across Europe. RESULTS: Malondialdehyde DNA adducts (M1dG) were associated with increased MN frequency in binucleated lymphocytes (MNBN), and exposure to androgenic, estrogenic, and dioxin-like compounds was associated with MN frequency in mononucleated lymphocytes (MNMONO), although no monotonic exposure-outcome relationship was observed. Lower frequencies of MNBN were associated with a 1-unit increase expression of PDCD11, LATS2, TRIM13, CD28, SMC1A, IL7R, and NIPBL genes. Gene expression was significantly higher in association with the highest versus lowest category of bulky and M1dG-DNA adducts for five and six genes, respectively. Gene expression levels were significantly lower for 11 genes in association with the highest versus lowest category of plasma AR CALUX® (chemically activated luciferase expression for androgens) (8 genes), ER? CALUX® (for estrogens) (2 genes), and DR CALUX® (for dioxins). Several SNPs (single-nucleotide polymorphisms) on chromosome 11 near FOLH1 significantly modified associations between androgen activity and MNBN frequency. Polymorphisms in EPHX1/2 and CYP2E1 were associated with MNBN. CONCLUSION: We measured in utero exposure to selected environmental carcinogens and circulating hormonally acting factors and detected associations with MN frequency in newborns circulating T lymphocytes. The results highlight mechanisms that may contribute to carcinogen-induced leukemia and require further research.

Dataset Information

Exposure to brominated trihalomethanes in water during pregnancy and micronuclei frequency in maternal and cord blood lymphocytes.

Publications

Exposure to brominated trihalomethanes in water during pregnancy and micronuclei frequency in maternal and cord blood lymphocytes.

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