Predisposing factors in occupational lung cancer: inorganic minerals and chromium.

Reactive oxygen species (ROS) have been implicated in the pathogenesis of cancer. Inhalation of inorganic minerals such as asbestos and crystalline silica, and metals such as arsenic, beryllium, chromium, nickel, and vanadium, may promote directly and indirectly enhanced generation of ROS at a persistent level in concert with chronic inflammation. Perpetual ROS generation can cause specific molecular changes resulting in the activation or inactivation of transcription factors that may alter gene expression leading to cell proliferation, differentiation, and carcinogenesis. The mechanisms involved in the signal transduction leading to these processes are the subject of intense investigation. In this review, some of the recent findings from our laboratories concerning key molecular events elicited by asbestos, crystalline silica, and chromium are presented. These include genotoxicity, DNA damage, lipid peroxidation, activation of transcription factors activator protein-1 (AP-1) or nuclear factor kappa B (NF-kappaB), and p53 or k-ras gene alterations. From these studies, it is evident that ROS signaling is critical for the responses of cytokines, growth factors, and activation or inactivation of transcription factors that promote carcinogenesis.