Rao N R, Snyder R
Rutgers University, Environmental and Occupational Health Sciences Institute, Piscataway, NJ 08855-1179, USA.
J Appl Toxicol. 1995 Sep-Oct;15(5):403-9. doi: 10.1002/jat.2550150511.
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.
我们研究了苯代谢物对苯二酚、对苯醌或1,2,4-苯三酚对HL-60细胞的细胞毒性、活性氧生成、过氧化氢（即氢过氧化物）产生和一氧化氮生成的影响。我们还研究了这些化合物对这些细胞中抗氧化酶和细胞内抗氧化剂的影响。发现苯代谢物对HL-60细胞的细胞毒性顺序为对苯醌>对苯二酚>苯三酚。暴露于苯代谢物后，超氧阴离子产生或一氧化氮生成的基础水平未观察到明显变化，但在用TPA刺激每种代谢物后，超氧化物显著增加，而在这些条件下，对苯二酚和对苯醌而非1,2,4-苯三酚增加了一氧化氮的产生。与对照相比，暴露于苯代谢物后，HL-60细胞的过氧化氢形成显著增加。对抗氧化酶和细胞内抗氧化剂的研究表明，苯代谢物抑制或降低了不同抗氧化机制的水平，从而导致这些细胞中自由基的积累，使它们易受氧化损伤。
