Reactive oxygen species and silica-induced carcinogenesis.

Although silica has recently been designated as a carcinogen, its mechanism of carcinogenesis is not fully understood. Recent studies suggest that free-radical reactions may play an important role in the initiation and progression of cancer. This article summarizes literature on the generation of reactive oxygen species (ROS) directly from silica and from silica-stimulated cells. It also summarizes information concerning the role of ROS in silica-induced DNA damage as well as in silica-induced cell proliferation, including the effects of silica on the activation of nuclear transcription factors, induction of growth factors and oncogene expression, redox regulation of the p53 tumor suppressor gene, induction of apoptosis, and division of damaged cells. Understanding the role of ROS in silica-mediated reactions may help develop therapeutic agents to block silica-induced free radical reactions and thus prevent or attenuate silica-induced carcinogenesis.