Katsifis S P, Shamy M, Kinney L P, Burns F J
Institute of Environmental Medicine, New York University Medical Center, 550 First Ave, New York, NY 10016, USA.
Mutat Res. 1998 Dec 3;422(2):331-7. doi: 10.1016/s0027-5107(98)00214-0.
Chemical interaction is of major concern in the assessment of risk by regulatory agencies. In the present study, treatment of human lymphocytes with NiSO4 (1-100 microM) or UV-light (200, 1000 ergs/mm2) induced micronuclei (MN) in a dose-dependent fashion. Statistical analysis of the interaction factor (IF), showed that combined treatments of Ni(II) (1-100 microM) with UV-light (200, or 1000 ergs/mm2) interacted antagonistically for the induction of MN. Recently we reported that Ni(II) (0.5-10 microM) with UV-light (200 or 1000 ergs/mm2) or Cr(VI) or X-rays interacted antagonistically for the induction of sister chromatid exchanges (SCE), in peripheral human lymphocytes. These observations suggest that nickel present in complex mixtures may reduce the response, even in the presence of strong MN or SCE inducers, and may lead, therefore, to an underestimate of chemical exposure as assessed by these assays. Furthermore, metals affecting certain microsteps in the process of DNA replication or repair (e.g., histones, polymerases, ligases) may have similar antagonistic effects. Further studies are therefore recommended.
在监管机构评估风险时,化学相互作用是主要关注的问题。在本研究中,用硫酸镍(1 - 100微摩尔)或紫外线(200、1000尔格/平方毫米)处理人淋巴细胞,以剂量依赖方式诱导微核(MN)。对相互作用因子(IF)的统计分析表明,镍(II)(1 - 100微摩尔)与紫外线(200或1000尔格/平方毫米)联合处理对微核诱导具有拮抗作用。最近我们报道,镍(II)(0.5 - 10微摩尔)与紫外线(200或1000尔格/平方毫米)或六价铬或X射线在人外周血淋巴细胞中对姐妹染色单体交换(SCE)的诱导具有拮抗作用。这些观察结果表明,即使在存在强微核或姐妹染色单体交换诱导剂的情况下,复杂混合物中存在的镍也可能降低反应,因此可能导致通过这些检测评估的化学暴露被低估。此外,影响DNA复制或修复过程中某些微步骤的金属(例如组蛋白、聚合酶、连接酶)可能具有类似的拮抗作用。因此建议进行进一步研究。