Protective effects of foods rich in carotenoids against DNA damages due to reactions of chemically induced triplet states of melanin derivatives

类胡萝卜素在我们的饮食中包含一组具有光保护作用的次生植物成分。人类干预研究已经证明了主要的类胡萝卜素--β-胡萝卜素、番茄红素和叶黄素--的光保护作用。摄入后，这些化合物被吸收并通过血流分布到目标组织(皮肤和眼睛)，在那里它们显示出预防效果。这些作用从机制上与它们的抗氧化特性有关，如猝灭光诱导的激发三重态分子或单态氧，清除包括超氧化物或过氧化脂质在内的活性氧物种，从而有助于防止光氧化DNA损伤。在紫外光照射下，DNA被氧化，并在依赖光的反应中生成环丁烷嘧啶二聚体(CPDS)。在时间尺度上，这些过程直接发生在光曝光之后。最近，已有研究表明，除了这些直接效应之外，还会启动所谓的暗反应，在该反应中会出现延迟(数小时)的CPD(暗CPD)的形成。在紫外线诱导的反应序列中，黑色素和活性氧物种的降解产物形成二氧杂环己烷，这些二氧杂环己烷分解生成激发的三重态羰基。当激发三重态猝灭时，形成暗CPD。多氯二苯并二恶英的形态取决于它们的形成方式，通过对其进行高效液相-质谱联用分析，可以区分直接形成的物种和延迟形成的物种。类胡萝卜素是激发的三重态羰基的有效猝灭剂，因此应该能抑制暗CPD的产生。在模型系统和细胞培养(黑素细胞、皮肤模型)中，来自饮食来源(胡萝卜、西红柿、南瓜)的类胡萝卜素将被用来研究它们对黑暗CPD形成的影响。关键方面是一种营养方法，以解决复杂食品系统的性质，抑制紫外线照射后生物定义的损害，并将光保护作用归因于关键成分和主要机制，即激发三重态的猝灭。

Carotenoids comprise a group of secondary plant constituents in our diet with photoprotective properties. Human intervention studies have proven the light-protective effects of the major carotenoids beta-carotene, lycopene and lutein. After ingestion, the compounds are absorbed and distributed via the blood stream to the target tissues (skin and eye) where they reveal preventive effects. These effects are mechanistically linked to their antioxidant properties such as quenching of light-induced excited triplet state molecules or singlet oxygen and scavenging of reactive oxygen species including superoxide or lipid peroxides, thus contributing to the prevention of photooxidative DNA damage. Upon UV-irradiation, DNA is oxidized and cyclobutane pyrimidine dimers (CPDs) are generated in light-dependent reactions. On a time scale, these processes occur directly after light-exposure. Recently, it has been shown that in addition to these direct effects, a so called dark reaction is initiated in which a time delayed (hours) formation of CPDs (dark CPDs) occurs. In a UV-induced reaction sequence, degradation products of melanin and reactive oxygen species form dioxetanes, which decompose to yield excited triplet carbonyls. Upon quenching of the excited triplet state, dark CPDs are formed. The pattern of the CPDs depends on their way of formation, and its analyses by means of HPLC-MS/MS allows to distinguish between directly and delayed formed species. Carotenoids are efficient quenchers of excited triplet carbonyls and thus should inhibit the generation of dark CPDs. In model systems and cell culture (melanocytes, skin model) carotenoids from dietary sources (carrots, tomatoes, squash) will be used to investigate their effects on the formation of dark CPDs. Key aspect is a nutritional approach to address the properties of complex food systems inhibiting biologically defined damages following UV exposure and attributing photoprotective effects to the key components and a major mechanism, namely quenching of excited triplet states.