Carotenoids as protectors against UVB induced cutaneous damage.

类胡萝卜素作为 UVB 引起的皮肤损伤的保护剂。

• 批准号: 8297633
• 负责人: TATIANA M OBERYSZYN
• 金额: $ 19.9万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8297633
• 关键词: Acute; Agriculture; American; Anti-Inflammatory Agents; Anti-inflammatory; Antioxidants; Basal cell carcinoma; Carotenoids; Chemopreventive Agent; Chronic; Clinical Investigator; Clinical Research; Collaborations; Consumption; Cutaneous; DNA Damage; Development; Diagnosis; Diet; Dietary Intervention; Disease; Dose; Ecology; Environmental Carcinogens; Epidemiologic Studies; Epidemiology; Female; Food; Freeze Drying; Gender; Human; Inbred HRS Mice; Inflammation; Inflammatory; Laboratories; Life Style; Malignant Neoplasms; Mediating; Mus; Ohio; Pathway interactions; Pre-Clinical Model; Property; Prostate; Reporting; Research; Risk; Sex Characteristics; Skin; Skin Cancer; Skin Carcinoma; Skin Neoplasms; Squamous cell carcinoma; Testing; The Sun; Time; Tomatoes; Translating; Tumor Promotion; UV induced; Ultraviolet Rays; United States; Universities; Woman; Work; base; cancer type; college; design; feeding; lycopene; male; men; phytoene; phytofluene; pre-clinical; prospective; response; sex; sun protection; tumor; tumor progression; ultraviolet; ultraviolet damage

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.

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100多万新病例。事实上，被诊断出患有某种皮肤癌的美国人将比所有其他癌症的总和还要多。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损害作用的途径不同，在男性皮肤中阻止紫外线诱导的炎症可能不像我们在女性皮肤中所显示的那样有效地减少肿瘤的发展。最近的研究已经描述了番茄摄入量与一些不同癌症的减少之间的相关性；然而，番茄摄入量对UVB诱导的皮肤癌发生的影响还没有被评估。本应用程序中的研究旨在测试一种假设，即与不食用番茄相比，食用含有类胡萝卜素番茄红素、植烯或植物荧烯的番茄将减少紫外线辐射造成的皮肤损害，最终导致肿瘤发展减少。我们还假设，将存在剂量-反应关系，即含有高水平植烯和植物荧烯的冷冻干燥陈皮番茄产品的饮食将比含有中等水平这些胡萝卜素的红色番茄产品提供更高水平的紫外线保护。此外，根据我们的初步研究，我们假设对番茄饮食的反应将存在性别差异。提出了两个具体目标。具体目标1将确定在橘色西红柿和/或红西红柿中饮食中摄入的植酸烯、植氟烯和番茄红素是否能不同程度地减少急性UVB暴露对雄性和雌性SKH-1小鼠皮肤的炎症和DNA损伤效应。具体目标2的研究将确定在橘色番茄和红番茄中摄入植酸烯、植氟烯和番茄红素对UVB诱导的雄性和雌性SKH-1小鼠皮肤肿瘤的促进和进展的不同化学预防作用。最终，我们希望与俄亥俄州立大学的临床研究人员合作，将我们的临床前发现转化为对人类的营养干预。 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)的影响 损失最早是在大约30年前报道的，在过去的几年里势头一直在增强。流行病学研究一再表明，食用西红柿和西红柿产品与降低患多种疾病的风险有关，包括各种癌症。然而，番茄的消费对紫外线诱导的皮肤癌发生的影响还没有报道。目前提案中的研究将利用我们的临床前紫外线诱导皮肤炎症和肿瘤发展的模型来确定饮食摄入两种不同类型的西红柿是否可以调节这些反应。