Carotenoids as protectors against UVB induced cutaneous damage.

描述（由申请人提供）： 紫外线B（UVB）是一种主要的环境致癌物，与非黑色素瘤皮肤癌（NMSC）的发生有关。这些皮肤肿瘤是人类最常见的癌症形式，每年在美国发现超过100万例新病例。事实上，更多的美国人将被诊断出患有某种形式的皮肤癌，而不是所有其他癌症的总和。流行病学研究表明，NMSC的发展存在性别差异，男性患基底细胞癌（BCC）的可能性是女性的两倍，患鳞状细胞癌（SCC）的可能性是女性的三倍。我们实验室的研究表明，紫外线在男性和女性皮肤中发挥其破坏作用的途径是不一样的，并且在男性皮肤中阻断紫外线诱导的炎症在减少肿瘤发展方面可能不如我们在女性皮肤中所显示的那样有效。最近的研究表明，食用番茄与减少一些不同癌症之间存在相关性;然而，食用番茄对UVB诱导的皮肤癌发展的影响尚未得到评估。本申请中的研究旨在检验以下假设：与不食用番茄相比，食用含有类胡萝卜素番茄红素、八氢番茄红素或六氢番茄红素的番茄将减少由紫外线辐射引起的皮肤损伤，最终导致肿瘤发展减少。我们还假设，将有一个剂量-反应关系，这样的饮食含有冷冻干燥番茄产品含有高水平的八氢番茄红素和六氢番茄红素将赋予更高水平的保护，防止紫外线损伤比红色番茄产品含有中等水平的这些类胡萝卜素。此外，根据我们的初步研究，我们假设对番茄饮食的反应存在性别依赖性差异。提出了两个具体目标。具体目标1将确定是否饮食消费的八氢番茄红素，六氢番茄红素，番茄红素和番茄和/或红番茄减少急性UVB暴露在男性和女性Skh-1小鼠皮肤差异的炎症和DNA损伤作用。具体目标2中的研究将确定从番茄和红番茄中摄入八氢番茄红素、六氢番茄红素和番茄红素对UVB诱导的雄性和雌性Skh-1小鼠皮肤肿瘤促进和进展的不同化学预防作用。最终，我们希望与俄勒冈州立大学的临床研究人员合作，将我们的临床前研究结果转化为人类的营养干预。 公共卫生相关性： 营养干预的概念，以保护皮肤免受紫外线（UV）光介导 大约在30年前首次报告了损害情况，在过去几年中，损害的势头越来越大。流行病学研究一再表明，番茄和番茄制品的消费与降低许多疾病的风险有关，包括各种癌症。然而，番茄消费对紫外线诱导的皮肤癌发展的影响尚未报道。当前提案中的研究将利用我们的紫外线诱导的皮肤炎症和肿瘤发展的临床前模型来确定两种不同类型的西红柿的饮食消费是否可以调节这些反应。

DESCRIPTION (provided by applicant): Ultraviolet light B (UVB) is a major environmental carcinogen that has been implicated in the development of non-melanoma skin cancers (NMSC). These skin tumors are the most common form of cancer in humans, with over 1 million new cases identified in the United States each year. In fact, more Americans will be diagnosed with some form of skin cancer than all other cancers combined. Epidemiological studies have shown that there are gender differences in the development of NMSC, with men being twice as likely to develop Basal Cell Carcinoma (BCC)and three times as likely to develop squamous cell carcinoma (SCC) as women. Studies from our laboratory suggest that the pathways by which UV exerts its damaging effects in male and female skin are not the same and that blocking UV-induced inflammation in male skin may not be as effective in decreasing tumor development as we have shown it to be in female skin. Recent studies have described a correlation between tomato consumption and a decrease of a number of different cancers; however, the effects of tomato consumption on UVB-induced skin cancer development have not been evaluated. The studies in this application are designed to test the hypothesis that the dietary consumption of tomatoes containing the carotenoids lycopene, phytoene, or phytofluene will reduce skin damage caused by UV radiation as compared to no tomato consumption, ultimately resulting in decreased tumor development. We also hypothesize that there will be a dose-response relationship such that diets containing freeze dried tangerine tomato products containing high levels of phytoene and phytofluene will confer a greater level of protection against UV damage than red tomato products containing an intermediate level of these carotenoids. Furthermore, based on our preliminary studies, we hypothesize that there will be gender-dependent differences in the response to the tomato diets. Two specific aims are proposed. Specific aim 1 will determine whether the dietary consumption of phytoene, phytofluene, and lycopene in tangerine tomatoes and/or red tomatoes reduces the inflammatory and DNA-damaging effects of acute UVB exposure differentially in male and female Skh-1 murine skin. Studies in specific aim 2 will determine the differential chemopreventive effects of the dietary consumption of phytoene, phytofluene, and lycopene in tangerine tomatoes and red tomatoes on UVB-induced tumor promotion and progression in male and female Skh-1 murine skin. Ultimately, we hope to translate our pre-clinical findings to nutritional interventions in humans in collaboration with clinical investigators at OSU. PUBLIC HEALTH RELEVANCE: The concept of nutritional intervention to protect the skin against ultraviolet (UV) light-mediated damage was first reported about 30 years ago and has been gaining momentum over the last several years. Epidemiological research has repeatedly shown that the consumption of tomatoes and tomato products is associated with a reduced risk of a number of diseases, including various types of cancers. However, the effects of tomato consumption on UV-induced skin cancer development have not been reported. The studies in the current proposal will make use of our pre-clinical model of UV-induced cutaneous inflammation and tumor development to determine if dietary consumption of two different types of tomatoes can modulate these responses.