Cytotoxicity of 1,2-diacetylbenzene in human neuroblastoma SHSY5Y cells is mediated by oxidative stress.
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.
Department of Biochemistry and Molecular Biology, Yeungnam University, Daegu 705-717, Republic of Korea. minsun@pusan.ac.kr
Min-Sun
MS
Kim
Min Kyeong
MK
Kim
Kwang Seok
KS
Kim
Jae Heun
JH
Chung
So Jung
SJ
Kim
Jung Hye
JH
Kim
Jae-Ryong
JR
Kim
Jaewon
J
Lee
Byung Pal
BP
Yu
Hae Young
HY
Chung
D000098:Acetophenones / Q000633:toxicity*; D000111:Acetylcysteine / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004785:Environmental Pollutants / Q000633:toxicity*; D005434:Flow Cytometry; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D009447:Neuroblastoma; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism
D000098:Acetophenones; D000975:Antioxidants; D004785:Environmental Pollutants; D017382:Reactive Oxygen Species; C048792:1,2-diacetylbenzene; D005978:Glutathione; D000111:Acetylcysteine