title: Chronic low level arsenic exposure evokes inflammatory responses and DNA damage.
abstract: The cross-sectional study investigated the impact of chronic low level arsenic (As) exposure (11-50μg/L) on CD14 expression and other inflammatory responses in rural women of West Bengal enrolled from control (As level <10μg/L; N, 131) and exposed area (As level 11-50μg/L, N, 142). Atomic absorption spectroscopy revealed that As level in groundwater was higher in endemic areas (22.93±10. 1 vs. 1.61±0.15, P<0.0001) and showed a positive correlation [Pearsons r, 0.9281; 95% confidence interval, 0.8192-0.9724] with As content in nails of the exposed women. Flow cytometric analysis showed that CD 14 expression on monocytes was significantly higher (P<0.001) in exposed women and positively correlated with groundwater As [Pearsons r, 0.9191; 95% confidence interval, 0.7584-0.9745]. Leucocytes and airway cells of As exposed women exhibited up regulation of an inflammatory mediator, tumor necrosis factor-α (TNF-α) and transcription factor, nuclear factor-κB (NF-κB) (P<0.0001). Plasma pro inflammatory cytokines like - TNF-α, interleukins (ILs) - IL-6, IL-8, IL-12 were elevated whereas anti-inflammatory cytokine IL-10 was depleted in the exposed women. Sputa of the exposed women had elevated activity of inflammatory markers - MMP-2 and MMP-9 whereas sera were observed with only increased activity of MMP-9. Airway cells of the exposed women had exacerbated DNA damage than control. Level of oxidative DNA adducts like 8-hydroxy-2'-deoxyguanosine (8OHdG) were also enhanced in plasma of exposed women. Therefore it might be indicated that low level As exposure elicited a pro-inflammatory profile which might have been contributed in part by CD14 expressing monocytes and prolong persistence of pulmonary and systemic inflammation might have promoted oxidative DNA damage in the rural women.
authors.affiliation: Receptor Biology and Tumor Metastasis, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700026, India.
authors.forename: Kaustav
authors.initials: K
authors.lastname: Dutta
authors.affiliation: Receptor Biology and Tumor Metastasis, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700026, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Prasad
authors.affiliation: Receptor Biology and Tumor Metastasis, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700026, India. Electronic address: donasinha2012@gmail.com.
authors.forename: Dona
authors.initials: D
authors.lastname: Sinha
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D001151:Arsenic / Q000032:analysis; D020261:Arsenic Poisoning / Q000235:genetics / Q000378:metabolism*; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000378:metabolism; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood; D004781:Environmental Exposure / Q000009:adverse effects* / Q000032:analysis; D005260:Female; D060587:Groundwater / Q000032:analysis; D006801:Humans; D007194:India; D018836:Inflammation Mediators / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D009262:Nails / Q000737:chemistry; D012424:Rural Population; D013183:Sputum / Q000378:metabolism; D055815:Young Adult
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D018950:Lipopolysaccharide Receptors; D016328:NF-kappa B; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D001151:Arsenic
keywords: CD14; Groundwater; Inflammation; Low arsenic exposure; Oxidative DNA damage