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

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 microM) disrupted cytoskeletal integrity and caused morphological changes. 1,2-DAB significantly decreased cell viability and induced cell cycle arrest in the G(1) 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.

• Authors: Min-Sun Kim, Min Kyeong Kim, Kwang Seok Kim, Jae Heun Chung, So Jung Kim, Jung Hye Kim, Jae-Ryong Kim, Jaewon Lee, Byung Pal Yu, Hae Young Chung
• Journal: Toxicology (Toxicology) Vol. 243 Issue 1-2 Pg. 216-23 (Jan 14 2008) ISSN: 0300-483X [Print] Ireland
• PMID: 18063464 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acetophenones
• Antioxidants
• Environmental Pollutants
• Reactive Oxygen Species
• 1,2-diacetylbenzene
• Glutathione
• Acetylcysteine

Topics

• Acetophenones (toxicity)
• Acetylcysteine (pharmacology)
• Antioxidants (pharmacology)
• Apoptosis (drug effects)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Environmental Pollutants (toxicity)
• Flow Cytometry
• Glutathione (pharmacology)
• Humans
• Microscopy, Electron, Scanning
• Microscopy, Fluorescence
• Neuroblastoma
• Oxidative Stress (drug effects)
• Reactive Oxygen Species (metabolism)