Project Summary (2000-2006)

Exposure to hazardous wastes containing metals can produce inflammation and oxidative stress in susceptible animal species and in humans. This project is testing the hypothesis that inflammatory cytokines and nitric oxides, as well as the resulting oxidative stress, are necessary for cell transformation, and that anti-inflammatory, anti-oxidant agents inhibit the transformation process. Nickel and arsenic, two seemingly different metals, have been chosen to test this hypothesis, because both contribute to oxidative stress and they share immunosuppressive properties. Experiments are being performed using an immortal but non-tumorigenic human osteoblast-like cell line (HOS) to investigate these effects. Additionally, researchers are assessing whether human lymphocytes of healthy people show inter-individual differences in their responses to Ni and As, and whether the most active and least toxic anti-inflammatories suppress these metal-induced cell transforming responses. This study is identifying which inflammatory factors are required for malignant cell transformation, which means will suppress this transformation after metal exposure, and which factors can provide a useful measure of inter-individual differences in responses to metal toxicants. These developments are applicable to future screenings of people exposed to hazardous wastes containing metals.