Luciferase assay: A powerful tool to determine toxic metal-induced NF- κB activation

After several decades of intensive research, scientists have accumulated a rich and complex body of knowledge revealing that most toxic metals or metal-containing particles from either environmental sources or occupational sources act as human carcinogens. ^1-4 Yet a detailed molecular mechanism(s) of metal-induced malignant transformation leading to cancer is still missing. Emerging evidence indicates that cellular transformation and tumorigenesis in humans is a multistep process that requires both nongenetic and genetic alterations that promote the transformation of normal human cells into highly malignant ones. ⁵ However, currently it is still not clear which step or steps are effectively targeted by metals. Certainly, nuclear factor- κ B (NF- κ B) activation is involved in the process of carcinogenic transformation of cells, but how metals affect the signal transduction pathways leading to the activation of NF- κ B is still poorly understood. It is unequivocal that oxidative stress resulting from metal-induced generation of reactive oxidative species (ROS) is an important mechanism for the activation of NF- κ B by metal. However, a ROS-independent effect of metals on the cellular signaling pathway and on genomic stability may also account for this process. ^6,7.