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Psycho-physiological stress and its effects on ultraviolet light induced inflammation, DNA damage, and skin carcinogenesis

Saul, Alison Nicole

Abstract Details

2007, Doctor of Philosophy, Ohio State University, Integrated Biomedical Science.
Skin cancer is the most common type of cancer in the United States and it is primarily caused by the exposure to ultraviolet-B radiation. Non-melanoma skin cancers, such as basal cell carcinoma and squamous cell carcinoma comprise the majority of skin cancer cases. Ultraviolet-B radiation induces a host of changes in the skin, the primary target of UVB, including inflammation, DNA damage, and eventually skin carcinogenesis. UVB radiation can also induce immunosuppression. This immunosuppression makes it less likely that the immune system will be able to respond efficiently to immunogenic tumors such as squamous cell carcinomas. Therefore, we would predict that factors that can affect cell-mediated immunity would also have a high likelihood of affecting SCC tumor development as well. Psycho-physiological stress is powerful modulator of immune system function as well. While short-term (acute) stress enhances cell-mediated immunity long-term (chronic) stress suppresses cell-mediated immunity. We have used these stressors in combination with UVB radiation to understand the effects of psychological stress on UVB induced inflammation, DNA damage, and ultimately SCC skin carcinogenesis. Using techniques such as immunohistochemistry, real-time PCR, flow cytometry, and ELISA, we found that acute stress reduced DNA damage, enhanced gene expression of Th1 cytokines and chemokines in the skin, and enhanced leukocyte traffic, primarily T cell, into the skin and sites of tumor formation. As a result of this, acute stress reduced SCC tumor development. In contrast to these results, we found that chronic stress increased DNA damage, decreased the gene expression of Th1 cytokines and chemokines in the skin, and decreased T cell infiltration into the skin and sites of tumor formation. As a result of this, chronic stress increased SCC tumor development. Finally, we examined anxiety levels in our mice and because we considered high anxiety as a type of innate chronic stress, we predicted that anxiety would produce the same types of effects in response to UVB as chronic stress. This was, in fact, the case as the high anxiety mice had reduced levels of Th1 cytokines and chemokines and also reduced T cell infiltration which caused increased SCC tumor development.
Tatiana Oberyszyn (Advisor)

Recommended Citations

Citations

  • Saul, A. N. (2007). Psycho-physiological stress and its effects on ultraviolet light induced inflammation, DNA damage, and skin carcinogenesis [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1172850801

    APA Style (7th edition)

  • Saul, Alison. Psycho-physiological stress and its effects on ultraviolet light induced inflammation, DNA damage, and skin carcinogenesis. 2007. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1172850801.

    MLA Style (8th edition)

  • Saul, Alison. "Psycho-physiological stress and its effects on ultraviolet light induced inflammation, DNA damage, and skin carcinogenesis." Doctoral dissertation, Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=osu1172850801

    Chicago Manual of Style (17th edition)