Semester

Spring

Date of Graduation

2005

Document Type

Dissertation

Degree Type

PhD

College

Davis College of Agriculture, Natural Resources and Design

Department

Biochemistry

Committee Chair

Val Vallyathan

Committee Co-Chair

Joginder Nath

Abstract

Heat shock protein 70 (Hsp70) expression has been reported to be a sensitive biomarker of cell stress. Arsenic (As), cadmium (Cd), mercury (Hg), chromium (Cr), nickel (Ni), vanadium (V), and manganese (Mn) are widely used and exposure to these metals is associated with the development of pulmonary disease. Our data showed that exposure to these metals resulted in a significant increase in cytotoxicity, apoptosis, and generation of reactive oxygen species (ROS) in a human bronchial cell line, BEAS-2B. However, increased Hsp70 expression was observed only in cells exposed to As, Cd, and Hg. To correlate changes associated with Hsp70 overexpression, cytotoxicity, lipid peroxidation, and ROS generation were measured. Exposure of BEAS-2B cells to As, Cd, and Hg was associated with an increase of cytotoxicity, Hsp70 protein and mRNA in a time- and dose-dependent manner. ROS generation was detected by ESR spectroscopy and confocal microscopy. Induction of Hsp70 protein expression was inhibited by catalase and NAC. These results suggest that cellular injury caused by As, Cd, and Hg is mediated through ROS generation resulting in the expression of Hsp70. Therefore, Hsp70 may prove to be a sensitive biomarker for As, Cd, and Hg exposure with correlative measurements of other biomarkers of oxidative stress in human serum. Extensive studies were undertaken in human serum samples obtained from welders and unexposed workers. Welding generates fumes that contain many toxic metals and several toxic gases. We investigated the effects of welding fumes on correlates of oxidative stress in serum of asymptomatic shipyard welders. Blood samples were collected from 197 welders and 150 unexposed office workers matched for age, sex and smoking. The serum was assayed for total protein, albumin, total antioxidant, manganese superoxide dismutase, aconitase, glutathione peroxidase (GPx), Hsp70, isoprostane, and ROS. Changes caused by welding were evaluated in three groups based on exposure duration i.e., 1--10, 11--20 and 21+ years of work. Welding was associated with increase in serum protein, GPx, aconitase, ROS generation and isoprostane levels compared to controls. The results suggest that welding exposure can cause oxidative stress in workers of significant magnitude to be measured by serum biomarkers.

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