Krebswissenschaft und -therapie

Chronic Low Level Arsenic Exposure Inflicts Pulmonary and Systemic Inflammation

Abstract

Dona Sinha, Bidisha Mukherjee, Banani Bindhani, Kaustav Dutta, Hirak Saha, Priyanka Prasad and Manas Ranjan Ray

Objective: To examine whether chronic low level arsenic (As) exposure (11-50 μg/L) from drinking water elicits inflammation and oxidative stress.

Methods: Never-smoking pre-menopausal women (n=267) from Nadia district, West Bengal, India, were enrolled into two groups (i) control (n=122, median age 39 yr) from villages with <10 μg/L of As in groudwater, and (ii) exposed (n=145, median age 38 yr) from the same district where the groundwater As was 11-50 μg/L. As in water was measured by atomic absorption spectrophtometry with vapour generation assembly. Sputum cytology and hematology were done by standard procedures. Enzyme-linked immunosorbent assays were used to measure tumor necrosis factor-alpha (TNF-α), interleukin-6, 8, 10, 12 (IL-6, IL-8, IL-10, IL-12) and C-reactive protein (CRP) in plasma and cortisol in serum. Serum nitric oxide (NO) was measured colorimetrically, myleperoxidase (MPO) and neutrophil elastase by spectrophotometry, reactive oxygen species (ROS) by flow cytometry, and inducible nitric oxide synthase (iNOS) by immunocytochemistry.

Results: As level in groundwater was higher in endemic areas (28.32 ± 13.51 vs. 2.72 ± 1.18, p<0.05), and exposed women had lower hemoglobin, leukocyte and erythrocyte levels but elevated platelet count than control and their sputum contained increased number of alveolar macrophages and inflammatory cells. In addition, they had elevated levels of TNF-α, IL-8, IL-6, IL-12, CRP, cortisol and NO but depleted level of IL-10 with excess generation of ROS and increased expression of iNOS in the airways. Neutrophils of As-exposed subjects had elevated levels of MPO and elastase. After controlling education and family income as potential confounders, the rise in pro-inflammatory mediators in blood and excess generation of ROS in the airways were positively associated with as levels in ground water.

Conclusion: Drinking of water contaminated with low level of as for long causes pulmonary and systemic inflammation and generates excess ROS in the airways.