title: Chronic nickel-induced DNA damage and cell death: the protection role of ascorbic acid.
abstract: High consumption of nickel-containing products leads to more exposure of humans to nickel and its by-products. Except the lethal effect of acute nickel poison, chronic nickel exposure is also harmful to humans, but the mechanism of chronic nickel-induced cytotoxicity remains unclear. Here, we found that long-term exposure of Ni(2+) led to significant DNA fragmentation, cell death, and reactive oxygen species (ROS) generation in human leukemia HL-60 cells. Induction of Ni(2+) on DNA fragmentation and cell death could be prevented by the antioxidants ascorbic acid (ASA) or N-acetyl-cysteine (NAC), or enhanced by H(2)O(2), indicating the involvement of ROS generation in the chronic nickel cytotoxicity in cells. Long-term exposure of mice to low Ni(2+) also led to a significant increase in both the ROS generation in the serum and the DNA fragmentation in the peripheral blood mononuclear cells (PBMC), while coadministration of ASA with Ni(2+) together significantly decreased both the DNA fragmentation and the ROS generation. Collectively, these results proved that ROS generation is at least one mechanism of the cytotoxicity of chronic nickel exposure, while ASA is probably useful for people to prevent the chronic nickel cytotoxicity, especially for those who work or live near a mining area or a factory related with nickel.
authors.affiliation: Shanxi Vocational Poly-tech College, Taiyuan 030006, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Jia
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D016923:Cell Death; D053938:DNA Fragmentation; D018922:HL-60 Cells; D006801:Humans; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009532:Nickel / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D009532:Nickel; D001205:Ascorbic Acid