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首页> 外文期刊>Archives of Toxicology >The positive response of Ty1 retrotransposition test to carcinogens is due to increased levels of reactive oxygen species generated by the genotoxins
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The positive response of Ty1 retrotransposition test to carcinogens is due to increased levels of reactive oxygen species generated by the genotoxins

机译：Ty1逆转位测试对致癌物的积极反应是由于基因毒素产生的活性氧水平升高

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摘要

In previous laboratory and environmental studies, the Ty1 short-term test showed positive responses (i.e. induced mobility of the Ty1 retrotransposon) to carcinogenic genotoxins. Here, we provide evidence for a causal relationship between increased level of reactive oxygen species and induction the mobility of the Ty1 retrotransposon. Results obtained in concentration and time-dependent experiments after treatment, the tester cells with carcinogenic genotoxins [benzo(a)pyrene, benzo(a)anthracene, ethylmethanesulfonate, formamide], free bile acids (chenodeoxycholic, lithocholic acids) and metals (arsenic, hexavelant chromium, lead) showed a simultaneous increase in both cellular level of the superoxide anions and Ty1 retrotransposition rates. Treatment with the noncarcinogenic genotoxins [benzo(e)pyrene, benzo(b)anthracen, anthracene], conjugated bile acids (taurodeoxycholic, glycodeoxycholic acids) and metals (zinc, trivalent chromium) did not change significantly superoxide anions level and Ty1 retrotransposition rate. The induction by carcinogens of the Ty1 mobility seems to depend on the accumulation of superoxide anions, since the addition of the scavenger N-acetylcysteine resulted in loss of both increased amount of superoxide anions and induced Ty1 retrotransposition. Increased hydrogen peroxide levels are also involved in the induction of Ty1 retrotransposition rates in response to treatment with carcinogenic genotoxins, as evidenced by disruption of YAP1 gene in the tester cells. It is concluded that the carcinogen-induced high level of reactive oxygen species play a primary and key role in determination the selective response of Ty1 test to carcinogenic genotoxins.
机译：在先前的实验室和环境研究中，Ty1短期测试显示对致癌基因毒素有积极反应（即Ty1逆转座子的诱导迁移）。在这里，我们提供了增加的活性氧水平与Ty1反转录转座子的迁移性之间因果关系的证据。处理后在浓度和时间依赖性实验中获得的结果是，测试细胞具有致癌性基因毒素[苯并（a），苯并（a）蒽，甲磺酸乙酯，甲酰胺]，游离胆汁酸（鹅去氧胆酸，石胆酸）和金属（砷，六价铬，铅）在细胞中超氧阴离子水平和Ty1逆转位速率上同时增加。用非致癌性基因毒素[苯并（e）py，苯并（b）蒽，蒽]，共轭胆汁酸（牛磺脱氧胆酸，糖脱氧胆酸）和金属（锌，三价铬）处理不会明显改变超氧阴离子水平和Ty1逆转位速率。致癌剂诱导的Ty1迁移似乎取决于超氧阴离子的积累，因为添加清除剂N-乙酰半胱氨酸会导致增加的超氧阴离子损失和诱导的Ty1逆转位。过高的过氧化氢水平也参与了对致癌基因毒素治疗的Ty1逆转位速率的诱导，这通过测试细胞中YAP1基因的破坏来证明。结论是，致癌物诱导的高水平活性氧在确定Ty1试验对致癌基因毒素的选择性反应中起着主要和关键作用。

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