The role of oxidative stress in chemical carcinogenesis.

作者：James E. Klaunig, Yawei Xu, Jeffrey Scott Isenberg, S Bachowski, Kyle L. Kolaja, Jinghui Jiang, D.E. Stevenson, Earl F. Walborg · 发表于：Environmental Health Perspectives · 年份：1998 · DOI：10.1289/ehp.98106s1289 · 被引用次数：511 · 研究领域：Antioxidant Activity and Oxidative Stress、Vitamin C and Antioxidants Research、Free Radicals and Antioxidants

Oxidative stress results when the balance between the production of reactive oxygen species (ROS) overrides the antioxidant capability of the target cell; oxidative damage from the interaction of reactive oxygen with critical cellular macromolecules may occur. ROS may interact with and modify cellular protein, lipid, and DNA, which results in altered target cell function. The accumulation of oxidative damage has been implicated in both acute and chronic cell injury including possible participation in the formation of cancer. Acute oxidative injury may produce selective cell death and a compensatory increase in cell proliferation. This stimulus may result in the formation of newly initiated preneoplastic cells and/or enhance the selective clonal expansion of latent initiated preneoplastic cells. Similarly, sublethal acute oxidative injury may produce unrepaired DNA damage and result in the formation of new mutations and, potentially, new initiated cells. In contrast, sustained chronic oxidative injury may lead to a nonlethal modification of normal cellular growth control mechanisms. Cellular oxidative stress can modify intercellular communication, protein kinase activity, membrane structure and function, and gene expression, and result in modulation of cell growth. We examined the role of oxidative stress as a possible mechanism by which nongenotoxic carcinogens may function. In studies with the selective mouse liver carcinogen dieldrin, a species-specific and dose-dependent d...