Cytotoxicity of 1,2-diacetylbenzene in human neuroblastoma SHSY5Y cells is mediated by oxidative stress

• Published in: Toxicology (Amsterdam) 2008-01, Vol.243 (1), p.216-223
• Main Authors: Kim, Min-Sun, Kim, Min Kyeong, Kim, Kwang Seok, Chung, Jae Heun, Kim, So Jung, Kim, Jung Hye, Kim, Jae-Ryong, Lee, Jaewon, Yu, Byung Pal, Chung, Hae Young
• Format: Article
• Language: English
• Subjects: 1,2-Diacetylbenzene; Acetophenones - toxicity; Acetylcysteine - pharmacology; Antioxidant; Antioxidants - pharmacology; Apoptosis - drug effects; Biological and medical sciences; Cell Cycle - drug effects; Cell Line, Tumor; Cell Survival - drug effects; Cytotoxicity; Emergency; Environmental Pollutants - toxicity; Flow Cytometry; Glutathione - pharmacology; Humans; Medical sciences; Microscopy, Electron, Scanning; Microscopy, Fluorescence; Neuroblastoma; Neurology; Oxidative Stress - drug effects; Reactive Oxygen Species - metabolism; ROS; SHSY5Y; Toxicology; Tumors of the nervous system. Phacomatoses
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/j.tox.2007.10.012

Abstract Environmental substances or metabolites induce neuronal damage through oxidative stress. Environmental organic solvent metabolite, 1,2-diacetylbenzene (1,2-DAB), treated rats develop limb weakness with neuropathological damage in both the central and peripheral nervous systems. In this experiment, we examined the relevance of 1,2-DAB-induced toxicity to increased oxidative stress using human dopaminergic neuroblastoma SHSY5Y cells. 1,2-DAB (4, 16, and 32 μM) disrupted cytoskeletal integrity and caused morphological changes. 1,2-DAB significantly decreased cell viability and induced cell cycle arrest in the G1 phase in a concentration-dependent manner. At higher concentration, it produced apoptosis. Pre-treatment of cells with the antioxidants, GSH or N -acetylcysteine (NAC), effectively blocked 1,2-DAB-mediated cytotoxicity including cell viability, and morphological changes. These results therefore suggest that oxidative stress is involved in environmental metabolite 1,2-DAB-mediated neurotoxicity and that antioxidant treatment can effectively protect the nervous system from environmental hazards.