“Understanding the potential toxicity of nanoparticles (NPs) is important to ensure that these new products do not impose harmful effects to human and environmental health. Paper I is a literature review in which we discuss characteristics of nanomaterials, with an emphasis on transition metal oxide nanoparticles that influence cytotoxicity. Identification of those properties may lead to the design of more efficient and safer nanosized products for various industrial purposes and provide guidance for assessment of human and environmental health risk. We then investigate biochemical and molecular mechanisms of cytotoxicity that include oxidative stress-induced cellular events and alteration of the pathways pertaining to intracellular calcium homeostasis. All the stresses lead to cell injuries and death. Furthermore, as exposure to nanoparticles results in deregulation of the cell cycle (i.e., interfering with cell proliferation). Paper II is about our original research in which we evaluated the differential cytotoxicity between nickel oxide (NiO) and nickel hydroxide Ni(OH)2 in human bronchoalveolar carcinoma (A549) and human hepatocellular carcinoma (HepG2) cell lines. Cellular viability assays revealed cell line-specific cytotoxicity in which nickel NPs were only toxic to A549 cells. Time-, concentration-, and particle-specific viability was observed in A549 cells. NP-induced oxidative stress triggered subsequent dissipation of mitochondrial membrane potential and induction of caspase-3 enzyme activity. The subsequent apoptotic events lead to reduction in cell number, though the contribution of necrosis to cell viability is unknown. In addition to cell death, suppression of cell proliferation contributes to play an essential role in regulating cell number. Collectively, the observed cell viability is a function of cell death and suppression of proliferation”--Abstract, page iv
