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一种在分子和细胞水平评估太阳紫外线光毒性的体外策略:在光保护评估中的应用。

An in vitro strategy to evaluate the phototoxicity of solar UV at the molecular and cellular level: application to photoprotection assessment.

作者信息

Marrot L, Belaidi J P, Chaubo C, Meunier J R, Perez P, Agapakis-Causse C

机构信息

L'Oreal Advanced Research, Life Sciences Research, Central Department of Product Safety, 1, av. E.-Schueller, 93600 Aulnay-sous-Bois, France.

出版信息

Eur J Dermatol. 1998 Sep;8(6):403-12.

PMID:9729050
Abstract

Skin cancers are among the most common human cancers and have an increasing incidence. The ultraviolet radiation components of sunlight play a major role in skin tumor induction and development. Cellular DNA has been identified as a target for most of the biological effects of UV, and the induction of photodamage is considered as the initiating step of photocarcinogenesis. Thus, effective photoprotection of DNA against harmful overex-posure to solar UV is a critical issue. The efficiency of a sunscreen is usually tested with respect to its ability to prevent skin erythema, but conceivably, more data are required at the molecular and cellular level in order to ascertain protection against photocarcinogenic risk. In the present study, we define a strategy based on the use of various in vitro models and solar-simulated light to evaluate photodamage and photoprotection: -Supercoiled circular plasmid DNA for detection of structural alterations. -The yeast Saccharomyces cerevisiae to evaluate cytotoxicity and genotoxicity. -The single-cell gel electrophoresis or comet assay to determine DNA damage and DNA repair in human keratinocytes. -p53 expression as a hallmark for genotoxic stress. -Induction of pigmentation in human melanocytes. In conditions where light source, spectrum and control of radiation delivery were precisely defined, we have demonstrated that the wide spectrum UVA sunscreen Mexoryl SX protects from the cytotoxicity and genotoxicity of solar UV.

摘要

皮肤癌是人类最常见的癌症之一,其发病率正在上升。阳光中的紫外线辐射成分在皮肤肿瘤的诱导和发展中起主要作用。细胞DNA已被确定为紫外线大多数生物学效应的靶点,光损伤的诱导被认为是光致癌作用的起始步骤。因此,有效地保护DNA免受太阳紫外线的有害过度照射是一个关键问题。防晒霜的功效通常根据其预防皮肤红斑的能力来测试,但可以想象,为了确定其对光致癌风险的防护作用,在分子和细胞水平上还需要更多数据。在本研究中,我们定义了一种基于使用各种体外模型和太阳模拟光来评估光损伤和光防护的策略:

  • 用于检测结构改变的超螺旋环状质粒DNA。

  • 用于评估细胞毒性和遗传毒性的酿酒酵母。

  • 用于确定人类角质形成细胞中DNA损伤和DNA修复的单细胞凝胶电泳或彗星试验。

  • p53表达作为遗传毒性应激的标志。

  • 人类黑素细胞中色素沉着的诱导。在精确界定光源、光谱和辐射传递控制的条件下,我们已经证明广谱UVA防晒霜麦素宁滤光环(Mexoryl SX)可保护细胞免受太阳紫外线引起的细胞毒性和遗传毒性。

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