Mechanisms of induction of chromosomal aberrations by hydroquinone in V79 cells
Mechanisms of induction of chromosomal aberrations by hydroquinone in V79 cells
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DOI：
10.1093/mutage/geg029
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发表时间：
2003-11-01
期刊：
影响因子：
2.7
通讯作者：
Rueff, J
中科院分区：
文献类型：
--
作者：
Silva, MDCU;Gaspar, J;Rueff, J
对苯二酚天然存在于细菌和植物中，也可用于商业用途。人类接触这种化合物可能是通过环境、职业、饮食和香烟烟雾暴露，以及暴露在苯中，苯可以被代谢成这种化合物。然而，接触这种化合物的主要来源是饮食，因为对苯二酚是许多食物中的一种天然化合物。对苯二酚可以被代谢成苯二酚，苯二酚是一种具有强烈的血液毒性、遗传毒性和致癌作用的化合物，也可以诱导自由基物种的形成，使细胞容易受到氧化损伤。为了阐明自由基物种在氢醌遗传毒性中的作用，我们研究了不同pH值(6.0、7.4和8.0)下V79细胞染色体的诱变和羟基自由基的产生，以及抗氧化酶[过氧化氢酶和超氧化物歧化酶(SOD)]对氢醌断裂效应的影响。结果表明，对苯二酚的断裂活性依赖于pH，表明在所用的实验条件下，去质子化是导致DNA损伤的基本步骤。S9混合物、超氧化物歧化酶或超氧化物歧化酶和过氧化氢酶的加入显著降低了细胞的裂解活性，提示超氧阴离子和过氧化氢参与了对苯二酚的遗传毒性。然而，在对苯二酚的自氧化过程中产生的其他物种，如半对苯二酚自由基或对苯二酚，似乎也在其遗传毒性中发挥作用，因为添加抗氧化酶(过氧化氢酶和超氧化物歧化酶)或S9混合物并不能完全取消所观察到的遗传毒性活性。这些结果表明，至少存在两种与该化合物的遗传毒性活性相关的机制。
Hydroquinone occurs naturally in bacteria and plants and it is also manufactured for commercial use. Human exposure to this compound can occur by environmental, occupational, dietary and cigarette smoke exposure and from exposure to benzene, which can be metabolized to this compound. However, the main source of exposure to this compound is dietary, since hydroquinone is a naturally occurring compound in many foods. Hydroquinone can be metabolized to benzoquinones, which are potent haematotoxic, genotoxic and carcinogenic compounds that can also induce the formation of radical species, predisposing cells to oxidative damage. In order to clarify the involvement of radical species in the genotoxicity of hydroquinone, the induction of chromosomal aberrations in V79 cells was studied along with the assessment of the production of hydroxyl radicals at different pH values (6.0, 7.4 and 8.0), as well as the effect of antioxidant enzymes [catalase and superoxide dismutase (SOD)] on the clastogenic effect of hydroquinone. The results obtained indicate that the clastogenic activity of hydroquinone is dependent on the pH, suggesting that deprotonation is a fundamental step leading to DNA lesions under the experimental conditions used. The addition of S9 mix, SOD or SOD and catalase significantly decreased the clastogenic activity, suggesting the involvement of superoxide anion and hydrogen peroxide in the genotoxicity of hydroquinone. However, other species generated in the auto-oxidation process of hydroquinone, such as the semiquinone radical or the quinone, also seem to play a role in its genotoxicity, since the addition of antioxidant enzymes (catalase and SOD) or S9 mix do not lead to a complete abolition of the observed genotoxic activity. These results suggest the existence of at least two mechanisms associated with the genotoxic activity of this compound.