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等效因子概念在呋喃香豆素混合物光毒性和遗传毒性中的应用。

Application of the equivalency factor concept to the phototoxicity and -genotoxicity of furocoumarin mixtures.

作者信息

Raquet Nicole, Schrenk Dieter

机构信息

Food Chemistry and Toxicology, University of Kaiserslautern, D-67663 Kaiserslautern, Germany.

Food Chemistry and Toxicology, University of Kaiserslautern, D-67663 Kaiserslautern, Germany.

出版信息

Food Chem Toxicol. 2014 Jun;68:257-66. doi: 10.1016/j.fct.2014.03.014. Epub 2014 Mar 26.

DOI:10.1016/j.fct.2014.03.014
PMID:24680798
Abstract

Furocoumarins (FCs) are natural constituents widely occurring in plants used as food or in phytomedicines, cosmetics, etc. Some FCs exert dermal photo-toxicity and -genotoxicity when combined with UVA irradiation. For a few congeners, skin tumor formation has been described in humans and laboratory animals. Since almost no information is available on the photo-toxic properties of several congeners, we analyzed the photo-cytotoxic, photo-mutagenic, and photo-clastogenic properties in V79 cells for thirteen naturally occurring FCs, and for the coumarin limettin. Furthermore, nine FC mixtures including one mixture based on the FC pattern of an Angelica archangelica extract were tested in the same assays. We found that the concept of relative potency factors for photo-cytotoxic, -mutagenic, and -clastogenicpotencies of FCs, setting the value for 5-methoxypsoralen at 1.00, was applicable to all congeners tested. The concept was used successfully to describe the photo-toxic properties of binary mixtures of 5- and 8-methoxypsoralen. Furthermore, the photo-genotoxic (photo-mutagenic and -clastogenic) properties of complex FC mixtures comprising up to nine different congeners could be predicted. These data suggest that FCs can differ widely in their photo-toxic and photo-genotoxic properties but show relatively strict additivity with respect to their on target-effects when occurring as complex mixtures.

摘要

呋喃香豆素(FCs)是广泛存在于用作食物的植物或植物药、化妆品等中的天然成分。一些FCs与紫外线A(UVA)照射联合时会产生皮肤光毒性和光致基因毒性。对于少数同系物,已在人类和实验动物中描述了皮肤肿瘤的形成。由于几乎没有关于几种同系物光毒性特性的信息,我们分析了13种天然存在的FCs以及香豆素欧芹酚甲醚在V79细胞中的光细胞毒性、光致突变性和光断裂性特性。此外,还在相同试验中测试了9种FC混合物,包括一种基于当归提取物FC模式的混合物。我们发现,将5-甲氧基补骨脂素的值设为1.00的FCs光细胞毒性、光致突变性和光断裂性相对效力因子的概念适用于所有测试的同系物。该概念成功用于描述5-和8-甲氧基补骨脂素二元混合物的光毒性特性。此外,还可以预测包含多达9种不同同系物的复杂FC混合物的光致基因毒性(光致突变性和光断裂性)特性。这些数据表明,FCs的光毒性和光致基因毒性特性可能有很大差异,但作为复杂混合物出现时,它们在靶效应方面表现出相对严格的加和性。

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