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复杂混合物中优先多环芳烃的遗传毒性。

The genotoxicity of priority polycyclic aromatic hydrocarbons in complex mixtures.

作者信息

White Paul A

机构信息

NRC Research Associate, Atlantic Ecology Division, United States Environmental Protection Agency, 27 Tarzwell Drive, Narragansett, RI 02882, USA.

出版信息

Mutat Res. 2002 Mar 25;515(1-2):85-98. doi: 10.1016/s1383-5718(02)00017-7.

Abstract

Risk assessment of complex environmental samples suffers from difficulty in identifying toxic components, inadequacy of available toxicity data, and a paucity of knowledge about the behavior of geno(toxic) substances in complex mixtures. Lack of information about the behavior of toxic substances in complex mixtures is often avoided by assuming that the toxicity of a mixture is simply the sum of the expected effects from each mixture component, i.e. no synergistic or antagonistic interactions. Although this assumption is supported by research investigating non-genotoxic end-points, the literature describing the behavior of genotoxic substances in complex mixtures is sparse and, occasionally, contradictory. In this study, the results of polycyclic aromatic hydrocarbon (PAH) analyses on freshwater bivalves were used to prepare realistic mixtures containing up to 16 PAHs. The SOS genotoxicity of the mixtures and each component were then assessed in an effort to evaluate the additivity of PAH genotoxicity. At nominal PAH concentrations above 1 microg/ml, observed genotoxic responses were far lower than those predicted under the assumption of additivity. At nominal concentrations below 0.75 microg/ml, differences are smaller and occasionally negligible, indicating that the genotoxicity of unsubstituted homocyclic PAHs is additive or slightly less than additive. Other researchers who have investigated the mutagenicity, carcinogenicity, and DNA binding activity of mixtures containing unsubstituted homocyclic PAHs have also reported additive effects. Therefore, the mutagenic risk posed by simple, well-characterized mixtures of priority PAHs can reasonably be estimated as the sum of the risks posed by the mixture components. Current data indicate that less-than-additive effects likely result from saturation of metabolic pathways needed to activate mutagenic PAHs.

摘要

对复杂环境样本进行风险评估存在诸多困难,包括难以识别有毒成分、现有毒性数据不足,以及对复杂混合物中基因毒性物质行为的了解匮乏。由于假定混合物的毒性仅仅是各混合物成分预期效应的总和,即不存在协同或拮抗相互作用,因此常常忽略了关于有毒物质在复杂混合物中行为的信息。尽管这一假设得到了针对非基因毒性终点研究的支持,但描述基因毒性物质在复杂混合物中行为的文献却很稀少,而且偶尔还相互矛盾。在本研究中,利用对淡水双壳贝类进行多环芳烃(PAH)分析的结果,制备了含有多达16种PAH的实际混合物。然后评估了这些混合物及其各成分的SOS基因毒性,以努力评估PAH基因毒性的加和性。在标称PAH浓度高于1微克/毫升时,观察到的基因毒性反应远低于在加和性假设下预测的反应。在标称浓度低于0.75微克/毫升时,差异较小,偶尔可忽略不计,这表明未取代的同环PAH的基因毒性具有加和性或略低于加和性。其他研究含有未取代同环PAH混合物的致突变性、致癌性和DNA结合活性的研究人员也报告了加和效应。因此,由简单且特征明确的优先PAH混合物所构成的致突变风险可以合理地估计为混合物各成分所构成风险的总和。目前的数据表明,低于加和性的效应可能是由于激活致突变PAH所需代谢途径的饱和所致。

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