Doctor of Philosophy, The Ohio State University, 2007, Integrated Biomedical Science
Non-melanoma skin cancer is the most prevalent form of cancer. The incidence of basal cell carcinoma is 2X higher and squamous cell carcinoma is 3X higher in males compared to females. Exposure to UVB is the primary agent responsible for the formation of NMSCs. While it is well documented that males spend more time out in the sun and use less sun protective measures, the potential of a biological contribution to these gender differences had not been previously evaluated. We therefore investigated the gender differences in the acute UVB induced inflammatory response and chronic UVB induced tumor formation in the hairless Skh-1 mouse model. Our studies demonstrated that acute exposure to UVB induced a cutaneous inflammatory response in both the male and female mice, however, the response was markedly lower in the males. After chronic exposure to UVB, the male mice exhibited enhanced carcinogenesis as they developed tumors earlier, developed more tumors, and developed larger tumors. Overall males had twice the tumor burden and more aggressive tumors. Interestingly, with the limited inflammatory response, the males exhibited elevated oxidative DNA damage and a limited antioxidant capacity allowing for more oxidative stress induced DNA damage. There is evidence that estrogen may convey a protective effect on the female gender. Topical estrogen decreased the acute inflammatory response in the female mice, yet enhanced the response in the males. Estrogen enhanced tumor multiplicity and tumor burden in the female mice, however, the tumors in both genders were less aggressive. Topical treatment with Faslodex, a complete anti-estrogen, increased tumor size in both genders and the tumors were more aggressive. Due to the gender differences in baseline antioxidant capacity, we examined the activity of catalase, glutathione peroxidase, glutathione reductase and glutathione s-transferase in the skin. These studies demonstrated that multiple enzymes contribute to the baseline diffe (open full item for complete abstract)
Committee: Tatiana Oberyszyn (Advisor)
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