Mechanisms for the induction of oxidative stress in Syrian hamster embryo cells by acrylonitrile
Mechanisms for the induction of oxidative stress in Syrian hamster embryo cells by acrylonitrile
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DOI：
10.1093/toxsci/67.2.247
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发表时间：
2002-06-01
影响因子：
3.8
通讯作者：
Klaunig, JE
中科院分区：
文献类型：
--
作者：
Zhang, HZ;Kamendulis, LM;Klaunig, JE
长期给予大鼠丙烯腈导致脑神经胶质肿瘤的发病率增加。最近的研究表明，丙烯腈诱导大鼠脑和培养的大鼠神经胶质细胞的氧化应激，丙烯腈还诱导叙利亚胚胎（SHE）细胞的形态学转化，伴随着氧化DNA的形成增加，以剂量依赖性的方式。SHE细胞中氧化应激的诱导机制尚未得到解决。本研究探讨了丙烯腈对SHE细胞中酶和非酶抗氧化剂的影响。用亚细胞致死剂量的丙烯腈（0、25、50和75 μ g/ml）处理SHE细胞4、24和48小时。丙烯腈（50 μ g/ml和75 μ g/ml）在所有时间点增加SHE细胞中活性氧的量。处理4 h后，SHE细胞中谷胱甘肽（GSH）被耗尽，过氧化氢酶和超氧化物歧化酶活性显著降低。这些抗氧化剂的抑制是暂时的，在24和48小时后恢复到对照值或更高。黄嘌呤氧化酶活性增加后，24和48小时的处理与丙烯腈。1-氨基苯并三唑，自杀性P450酶抑制剂，减弱丙烯腈对SHE细胞中过氧化氢酶和黄嘌呤氧化酶的影响，表明丙烯腈需要P450代谢才能对这些酶产生影响。其他研究表明，在没有代谢来源的情况下，丙烯腈对过氧化氢酶或超氧化物歧化酶活性没有影响。这些结果表明，丙烯腈的氧化应激的诱导涉及的抗氧化剂的时间减少和黄嘌呤氧化酶活性的增加，这是由丙烯腈的氧化代谢介导的。
Chronic administration of acrylonitrile to rats resulted in an increase in the incidence of glial neoplasms of the brain. Recent studies have shown that acrylonitrile induces oxidative stress in rat brain and cultured rat glial cells, Acrylonitrile also induces morphological transformation concomitant with an increase in the formation of oxidized DNA in Syrian Hamster Embryo (SHE) cells in a dose-dependent manner. The mechanism for the induction of oxidative stress in SHE cells remains unresolved. The present study examined the effects of acrylonitrile on enzymatic and nonenzymatic antioxidants in SHE cells. SHE cells were treated with subcytolethal doses of acrylonitrile (0, 25, 50, and 75 mug/ml) for 4, 24, and 48 h. Acrylonitrile (50 mug/ml and 75 mug/ml) increased the amount of reactive oxygen species in SHE cells at all time points. Glutathione (GSH) was depleted and catalase and superoxide dismutase activities were significantly decreased in SHE cells after 4 h of treatment. The inhibition of these antioxidants was temporal, returning to control values or higher after 24 and 48 h. Xanthine oxidase activity was increased following 24 and 48 h treatment with acrylonitrile. 1-aminobenzotriazole, a suicidal P450 enzyme inhibitor, attenuated the effects of acrylonitrile on catalase and xanthine oxidase in SHE cells, suggesting that P450 metabolism is required for acrylonitrile to produce its effects on these enzymes. Additional studies showed that in the absence of metabolic sources acrylonitrile had no effect on either catalase or superoxide dismutase activity. These results suggest that the induction of oxidative stress by acrylonitrile involves a temporal decrease in antioxidants and increase in xanthine oxidase activity that is mediated by oxidative metabolism of acrylonitrile.