REACTIVE OXYGEN SPECIES AND SILICA-INDUCED CARCINOGENESIS

Although silica has recently been designated as a carcinogen, its mech anism of carcinogenesis is not fully understood. Recent studies sugges t that free-radical reactions may play an important role in the initia tion and progression of cancer. This article summarizes literature on the generation of reactive oxygen species (ROS) directly from silica a nd from silica-stimulated cells. It also summarizes information concer ning the role of ROS in silica-induced DNA damage as well as in silica -induced cell proliferation, including the effects of silica on the ac tivation 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. Understa nding the role of ROS in silica-mediated reactions may help develop th erapeutic agents to block silica-induced free radical reactions and th us prevent or attenuate silica-induced carcinogenesis.