Food, Agricultural, and Environmental Sciences (FAES): 1st Place (The Ohio State University Edward F. Hayes Graduate Research Forum)Background: Vitamin D has received recent attention as a nutrient in which a large portion of Americans may be deficient. Vitamin D is a unique “essential” nutrient in that it can be produced endogenously in the skin via UVB irradiation of 7-dehydrocholesterol, or taken in from the diet. Although it is well established that vitamin D plays a role in bone health, a growing body of evidence suggests that it may also have a role in chronic diseases, including several types of cancer. Vitamin D is not naturally present in many foods although some foods including dairy products and ready to eat cereals are fortified. Some researchers recommend that individuals receive approximately 5 to 15 minutes of unprotected sun exposure several times a week in order to produce sufficient amounts of vitamin D, yet unprotected sun exposure is also a risk factor for skin cancer. Cell studies have demonstrated that 1,25-dihydroxyvitamin D, the active metabolite of vitamin D, has an inhibitory effect on skin cancer initiation, but cancerous cells lose sensitivity to the growth regulating properties of the compound. These recent reports indicate an important biological role of vitamin D metabolites in skin cancer development, but there have been no studies on the disease measuring these compounds in skin. This is primarily due to the challenging nature of this analysis and need for highly sensitive and sophisticated analytical instrumentation.
Purpose/Rationale: Since vitamin D may have a role in the prevention of skin cancer, and the UVB exposure needed for endogenous synthesis of the vitamin is a risk factor for the disease, the effects of dietary vitamin D on the development of skin cancer is a critical area of investigation. However, before results can be translated to humans, appropriate animal models of skin cancer need to be investigated. The purpose of this research is to measure the levels of biologically relevant vitamin D metabolites in the skin and serum of mice fed escalating doses of vitamin D.
Research Methods: To evaluate the effects of dietary vitamin D on non-melanoma skin cancer (NMSC), 150 Skh-1 hairless, but immunocompetent, mice were placed on diets with escalating doses of the vitamin for 29 weeks. The Skh-1 mouse is a well-recognized model of NMSC. Equal numbers of male and female mice were assigned to each dietary level of vitamin D (25, 150, 1000 IU). Within each dietary level, n=15 mice were exposed to UVB light three times per week for the last 25 weeks of the study, and n=10 mice were abstained from the treatment. The UVB exposure given to the mice was one minimal erythemic dose, which is equivalent to a light sunburn. Vitamin D metabolite levels will be measured in the serum and skin of the mice using high performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS), a sensitive and advanced analytical technique. The estimated levels of these compounds in the skin are quite low, thus extracts from skin samples will be derivatized with 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD), allowing more efficient and sensitive analysis of the vitamin D metabolites.
Predicted Findings: We expect to see increased vitamin D metabolites in samples from mice supplemented with the nutrient. A dose-dependent increase in specific metabolites is also expected.
Implications: The levels of vitamin D-related compounds in the tissues and serum of mice from this study will be correlated with previously evaluated cancer outcomes. This will be the first study of its kind to measure vitamin D metabolites in murine skin using HPLC-MS/MS in an effort to elucidate the influence of dietary vitamin D on NMSC.A five-year embargo was granted for this item
