Semester

Fall

Date of Graduation

2010

Document Type

Thesis

Degree Type

MS

College

Eberly College of Arts and Sciences

Department

Biology

Committee Chair

Bingyun Li.

Abstract

Hard metal or cemented carbide consists of a powder mixture of 80 to 90% of tungsten carbide (WC) and 5 to 10% of metallic cobalt (Co). Nanoparticles are engineered structures with one dimension of at least 100 nanometers or smaller. The small size results in properties that may be substantially different from particles of the same composition in the micrometer scale. It has been demonstrated that the inhalation of hard metal particles may cause an interstitial pulmonary disease and lung cancer, the mechanism of which involves an interaction between Co and WC particles, the generation of reactive oxygen species, and oxidant-induced DNA-damage (1,2,3,4). However, the effect of WC-Co on biologic responses remains to be elucidated. In this study, we analyzed the effects of WC-Co nanoparticles in regulating production of reactive oxygen species (ROS), activation of AP-1, NF-kappaB, VEGF, AKT or ERK, and angiogenesis. We also tested the effect of fine- and nano-sizes of WC-Co with equal surface area on ROS production and the activation of AKT and ERK.;Results show that WC-Co nanoparticles at 5 microg/cm2 induce ROS production which activates AKT and ERK signaling pathways in lung epithelial cells. ROS also increased transcriptional activation of AP-1, NF-kappaB, as well as VEGF (via AKT and ERK1/2 activation); while the fine size of WC-Co particles at the same concentration did not have significant effect. However, at high concentrations, fine-size WC-Co particles also induced ROS production, and AKT and ERK1/2 activation. WC-Co nanoparticles also induced angiogenesis in cells. These results identify multiple signaling pathways that are activated by WC-Co nanoparticle treatment, and elucidate the potential molecular mechanisms of their effects on the cells. This information may be useful for preventing potential damage from WC-Co particle exposure in the future.

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