Knadle S
Cancer Res. 1985 Oct;45(10):4853-7.
Hydroquinone, a metabolite of benzene, and acetaldehyde, a metabolite of ethanol, induce sister chromatid exchanges (SCEs) at relatively high concentrations. Because both compounds are reported to form glutathione conjugates, experiments were carried out to see if there was a synergistic effect when lower concentrations of both chemicals were added to human lymphocyte cultures. Hydroquinone (40 microM) increased SCEs in some individuals but not in others. However, the rate of SCE was more than doubled when cells were pretreated with diethyl maleate, which transiently depletes cellular glutathione. Acetaldehyde by itself increased SCEs at 100 microM, but it increased SCEs at 1 microM in the presence of diethyl maleate. When various concentrations of acetaldehyde were added to cultures containing 40 microM hydroquinone, synergism in the induction of SCEs was observed. The lowest effective concentration of acetaldehyde varied among individuals from 1 to 100 microM. These observations suggest that glutathione is involved in the detoxification of hydroquinone and acetaldehyde in lymphocytes and that the simultaneous presence of both chemicals may saturate this mechanism and thus increase their genotoxic potency. Genetic differences in glutathione metabolism may govern the concentration of acetaldehyde at which synergism occurs in different individuals.
对苯二酚是苯的代谢产物，乙醛是乙醇的代谢产物，它们在相对高浓度时会诱导姐妹染色单体交换（SCEs）。由于据报道这两种化合物都会形成谷胱甘肽共轭物，因此开展了实验，以观察当将两种化学物质的较低浓度添加到人类淋巴细胞培养物中时是否存在协同效应。对苯二酚（40微摩尔）在一些个体中增加了SCEs，但在其他个体中则没有。然而，当细胞用马来酸二乙酯预处理时，SCE的发生率增加了一倍多，马来酸二乙酯会短暂耗尽细胞内的谷胱甘肽。乙醛本身在100微摩尔时会增加SCEs，但在马来酸二乙酯存在的情况下，它在1微摩尔时就会增加SCEs。当将不同浓度的乙醛添加到含有40微摩尔对苯二酚的培养物中时，观察到在诱导SCEs方面存在协同作用。乙醛的最低有效浓度在个体之间从1到100微摩尔不等。这些观察结果表明，谷胱甘肽参与淋巴细胞对对苯二酚和乙醛的解毒作用，并且这两种化学物质同时存在可能会使该机制饱和，从而增加它们的遗传毒性效力。谷胱甘肽代谢的遗传差异可能决定了不同个体中发生协同作用时乙醛的浓度。
