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辛甲氧肉桂酸调节基因表达,防止环丁烷嘧啶二聚体形成,但不能防止 UV 暴露的人细胞系中的氧化 DNA 损伤。

Octyl methoxycinnamate modulates gene expression and prevents cyclobutane pyrimidine dimer formation but not oxidative DNA damage in UV-exposed human cell lines.

机构信息

Department of Chemical Toxicology, Division of Environmental Medicine, Norwegian Institute of Public Health, Nydalen, NO-0403 Oslo, Norway.

出版信息

Toxicol Sci. 2010 Apr;114(2):272-84. doi: 10.1093/toxsci/kfq005. Epub 2010 Jan 13.

Abstract

Octyl methoxycinnamate (OMC) is one of the most widely used sunscreen ingredients. To analyze biological effects of OMC, an in vitro approach was used implying ultraviolet (UV) exposure of two human cell lines, a primary skin fibroblast (GM00498) and a breast cancer (MCF-7) cell lines. End points include cell viability assessment, assay of cyclobutane pyrimidine dimers (CPDs) and oxidated DNA lesions using alkaline elution and lesion-specific enzymes, and gene expression analysis of a panel of 17 DNA damage-responsive genes. We observed that OMC provided protection against CPDs, and the degree of protection correlated with the OMC-mediated reduction in UV dose. No such protection was found with respect to oxidative DNA lesions. Upon UV exposure in the presence of OMC, the gene expression studies showed significant differential changes in some of the genes studied and the expression of p53 protein was also changed. For some genes, the change in expression seemed to be delayed in time by OMC. The experimental approach applied in this study, using a panel of 17 genes in an in vitro cellular system together with genotoxicity assays, may be useful in the initial screening of active ingredients in sunscreens.

摘要

辛基甲氧基肉桂酸酯(OMC)是最广泛使用的防晒霜成分之一。为了分析 OMC 的生物学效应,采用体外方法对两种人细胞系(原代皮肤成纤维细胞[GM00498]和乳腺癌[MCF-7]细胞系)进行紫外线(UV)暴露。终点包括细胞活力评估、使用碱性洗脱和损伤特异性酶检测环丁烷嘧啶二聚体(CPDs)和氧化 DNA 损伤,以及对 17 个 DNA 损伤反应基因的基因表达分析。我们观察到 OMC 对 CPDs 提供了保护,保护程度与 OMC 介导的 UV 剂量减少相关。对于氧化 DNA 损伤,没有发现这种保护。在存在 OMC 的 UV 暴露下,基因表达研究显示一些研究基因的表达发生了显著差异,p53 蛋白的表达也发生了变化。对于一些基因,OMC 似乎使表达的变化在时间上延迟。本研究应用的实验方法,在体外细胞系统中使用 17 个基因的基因表达谱以及遗传毒性检测,可能有助于防晒霜中活性成分的初步筛选。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e412/2840218/d21a139de219/toxscikfq005f01_3c.jpg

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