Oxidative modifications produced in HL-60 cells on exposure to benzene metabolites.
We have studied the effects of the benzene metabolites hydroquinone, p-benzoquinone or 1,2,4-benzenetriol on cytotoxicity, active oxygen formation, hydrogen peroxide (i.e. hydroperoxide) production and nitric oxide formation in HL-60 cells. We also examined the effects of these compounds on antioxidant enzymes and intracellular antioxidants in these cells. The cytotoxicity of benzene metabolites to HL-60 cells was found to be of the order of p-benzoquinone>hydroquinone>benzenetriol. No appreciable changes in the basal levels of either superoxide anion production or nitric oxide formation were observed following exposures to the benzene metabolites, but significant increases in superoxide were seen on stimulation with TPA for each metabolite, whereas hydroquinone and p-benzoquinone, but not 1,2,4-benzenetriol, increased nitric oxide production under these conditions. Following exposure to the benzene metabolites, HL-60 cells showed significant rises in hydrogen peroxide formation compared to controls. The study of antioxidant enzymes and intracellular antioxidants suggested that the benzene metabolites inhibit or reduce the levels of different antioxidant mechanisms and, thereby, cause the accumulation of free radicals in these cells predisposing them for oxidative damage.
Rao
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Rutgers University, Environmental and Occupational Health Sciences Institute, Piscataway, NJ 08855-1179, USA.
Snyder
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D001205:Ascorbic Acid / Q000378:metabolism; D016227:Benzoquinones / Q000633:toxicity*; D002374:Catalase / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D018922:HL-60 Cells / Q000187:drug effects*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D006873:Hydroquinones / Q000009:adverse effects* / Q000633:toxicity*; D007951:Leukemia, Myeloid / Q000473:pathology; D009153:Mutagens / Q000009:adverse effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D018384:Oxidative Stress; D009195:Peroxidase / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D016227:Benzoquinones; D006873:Hydroquinones; D009153:Mutagens; D017382:Reactive Oxygen Species; D013481:Superoxides; C013038:hydroxyhydroquinone; D009569:Nitric Oxide; C004532:quinone; D006861:Hydrogen Peroxide; D002374:Catalase; D009195:Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione; D001205:Ascorbic Acid; C031927:hydroquinone