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.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Exploratory/Developmental Grants (R21)
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Chemo/Dietary Prevention Study Section (CDP)
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Agelli, Maria
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Ohio State University
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Cooperstone, Jessica L; Tober, Kathleen L; Riedl, Ken M et al. (2017) Tomatoes protect against development of UV-induced keratinocyte carcinoma via metabolomic alterations. Sci Rep 7:5106
Kopec, Rachel E; Schick, Jonathan; Tober, Kathleen L et al. (2015) Sex differences in skin carotenoid deposition and acute UVB-induced skin damage in SKH-1 hairless mice after consumption of tangerine tomatoes. Mol Nutr Food Res 59:2491-501