Probing Sunscreen Failure Through Energy Transfer to DNA

通过将能量转移到 DNA 来探究防晒霜的失效

• 批准号: 6439727
• 负责人: THOMAS M NORDLUND
• 金额: $ 7.18万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-02-01 至 2004-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6439727
• 关键词: DNA; aminopurine; atomic absorption spectrometry; cancer prevention; fluorescence spectrometry; nucleoside analog; oligonucleotides; phenylcarboxylate; pteridines; radiation carcinogen; radiation carcinogenesis; radiation genetics; radiation protection; radiochemistry; sunscreens; tissue /cell culture; ultraviolet radiation

DESCRIPTION (provided by applicant): The aim of this project is to determine if sunscreens can fail to protect against UV damage by transferring absorbed UV energy to DNA. This project has three immediate goals (I) measure the interaction of sunscreen agents (e.g, octyl methoxycinnamate) with DNA through fluorescence and absorption spectroscopy; (ii) select the most favorable fluorescent DNA base analog- 2-aminopurine (2AP), or one of the pteridine-nucleoside analogs ("PNA's", M. Hawkins, Pediatric Branch, NCI)-to act as an energy acceptor from sunscreen; (iii) measure the efficiency of UV-excited energy transfer from active sunscreen agents to DNA and from DNA to sunscreen. In support of these goals, study of the dependence of energy transfer in DNA as a function of DNA length and conformation must continue. Sunscreens efficiently absorb UV radiation which can cause DNA damage in skin. The most favorable disposal mechanism for this absorbed energy is molecular internal conversion, leading to harmless heat dissipation. Studies of unfavorable energy-disposal mechanisms (e.g., radical and singlet oxygen formation) have been done to determine whether these processes, though rare, may contribute to DNA damage and the (bottom-line) failure of sunscreens to reduce the incidence of skin cancer in society. We will measure energy transfer, also an energy-dissipation mechanism, between sunscreen agents and DNA under in vitro conditions to determine the efficiency of transfer. Sunscreen agents can quickly be screened for unfavorable interaction with DNA, once protocols have been optimized. The next step would be to determine whether the in vitro interaction between sunscreen and DNA occurs in vivo. We have described 2AP-sensed base-to-base energy transfer in DNA in detail and, more recently, measured spectra of PNA-DNA from the Hawkins group. Neighboring bases (esp. adenine), base stacking, double helix formation and other DNA interactions cause spectroscopic changes that can be measured with commonly available absorption and fluorescence spectrophotometers. Spectral shift analysis (previously developed) as a function of temperature and solvent properties, as well as time-resolved fluorescence measurements will be performed to obtain native DNA spectroscopic signatures. Changes upon addition of sunscreen can then be precisely measured and the efficiency of energy transfer (or other interaction) determined (Xu and Nordlund, 2000). DNA damage would be directly proportional to this efficiency.

描述（由申请人提供）： 这个项目的目的是确定防晒霜是否不能保护 通过将吸收的紫外线能量转移到DNA来抵抗紫外线损伤。这个项目 三个直接目标（I）测量防晒剂的相互作用（例如， 甲氧基肉桂酸辛酯）与DNA通过荧光和吸收 （ii）选择最有利的荧光DNA碱基类似物- 2-氨基嘌呤（2AP）或蝶啶-核苷类似物（“PNA's”，M. Hawkins，Pediatric分支，NCI）-作为来自防晒霜的能量受体; (iii)测量UV激发的能量从活性物质转移的效率， 从防晒剂到DNA，再从DNA到防晒霜。为了支持这些目标， 研究DNA中能量转移对DNA长度的依赖性 而构造必须继续。防晒霜有效吸收紫外线辐射 会导致皮肤DNA损伤最有利的处置机制， 这种吸收的能量是分子内部转换，导致无害的 散热研究不利的能源处置机制（例如， 自由基和单线态氧的形成），以确定 这些过程虽然罕见，但可能导致DNA损伤， （底线）防晒霜未能降低皮肤癌的发病率， 社会我们将测量能量传递，也是能量耗散 在体外条件下，防晒剂和DNA之间的作用机制， 决定了转移的效率。防晒剂可以快速筛选 与DNA的不利相互作用，一旦协议已经优化。的 下一步将是确定是否在体外相互作用之间 防晒霜和DNA发生在体内。我们已经描述了2AP感测的基到基 能量转移的DNA的细节，最近，测量光谱的 来自霍金斯组的PNA-DNA。相邻碱基（特别是腺嘌呤），碱基 堆叠、双螺旋形成和其他DNA相互作用导致 光谱变化，可以用常用的吸收测量 和荧光光度计。光谱位移分析（以前 开发）作为温度和溶剂性质的函数，以及 将进行时间分辨荧光测量以获得天然DNA 光谱特征添加防晒霜后的变化可以 精确测量和能量转移（或其他）的效率 相互作用）（Xu和Nordlund，2000）。DNA损伤会直接 与这种效率成正比。