환경변이원 중금속 니켈에 의해 유발되는 분자독성기전에 대한 고찰

Abstract

Nickel (Ni) is a widely distributed industrial metal which can expose to human through polluted environments including nickel refining, electroplating, and welding industries. Ni exposure can cause a variety of pathological cellular effects through generation of reactive oxygen species (ROS), genotoxicity, inhibition of Ni-binding proteins, dysregulation of cell cycle control and apoptosis and DNA repair inhibition. Ni-induced ROS can lead to DNA damage, which can produce 8-oxo-dG, and triggers cell signaling pathways involve in cellular proliferation, apoptosis, and transformation. Furthermore, accumulation of nickel into the cells has negative impact on genetic materials, particularly on chromosome, resulting in chromosomal deletion, aberration, and regional decondensation. Nickel compounds alsomodulate gene expression, including c-myc, proto-oncogene whose product play role in carcinogenesis. Recent studies have shown that many proteins with strong affinity to Ni are involved in nickel transport, detoxification and excretion. Moreover, binding ability of Ni to particular proteins crucial for cellular functioning raises the possibility to change in homeostasis. Of interest, inhibition of DNA repair by nickel compounds probably causes cell death and mutation. The present review will provide information on the molecular and cellular toxicity of heavy metal nickel as one of most concerning environmental carcinogens.