UVB Exposure and Topical Estrogen Effects on the Development of Skin Cancer in a Pre- and Post-Menopausal Mouse Model
| Main Author: | |
|---|---|
| Language: | English |
| Published: |
The Ohio State University / OhioLINK
2012
|
| Subjects: | |
| Online Access: | http://rave.ohiolink.edu/etdc/view?acc_num=osu1337631752 |
| id |
ndltd-OhioLink-oai-etd.ohiolink.edu-osu1337631752 |
|---|---|
| record_format |
oai_dc |
| spelling |
ndltd-OhioLink-oai-etd.ohiolink.edu-osu13376317522021-08-03T06:05:02Z UVB Exposure and Topical Estrogen Effects on the Development of Skin Cancer in a Pre- and Post-Menopausal Mouse Model Creamer, Michelle Biomedical Research UVB skin cancer estrogen SKH1 Ultraviolet light (UV) is the most common complete carcinogen which we are exposed to on a daily basis that initiates and promotes tumor development and growth in the skin. Thus, multiple exposures to UV radiation from the sun can increase the incidence of skin cancer. Estrogen based hormone replacement therapy is now prescribed as a topical ointment. Estrogen, a known carcinogen, has been linked to increased risks of various reproductive systems cancers. Prior to this study, the effects of topical estrogen applied to sun exposed areas on the development of skin cancer had not been extensively studied. The specific aims of this study are twofold: (1) to determine the acute effects of topical estrogen on UVB induced inflammation, DNA damage, and repair and (2) to investigate the potential carcinogenic effect of topical estrogen on chronically UVB exposed skin in pre-menopausal and post-menopausal mouse models of human disease. We hypothesized that previously UVB irradiated skin treated with topical estrogen (10nmol) would result in increased inflammation and DNA damage acutely and ultimately result in increased tumor burden and severity. For the acute study, SKH1 mice were irradiated with UVB light once, treated topically with vehicle, Surgilube®, or estrogen and sacrificed at 24, 48, 72, or 96 hours (n=48). In the chronic study, mice were irradiated three times a week for 10 weeks (n=55). They were then randomized into two groups and underwent either surgical removal of their ovaries or a sham surgical procedure simulating pre- and post-menopausal conditions. These two groups were further randomized into 4 groups and treated topically with estrogen or Surgilube® three times a week for 15 weeks. Inflammatory mediators, myeloperoxidase, hydrogen peroxide, and prostaglandin E2 (PGE2) as well as markers of DNA damage, cyclobutane pyrimidine dimers and p53 were measured in the acute and chronic studies. Tumor growth was measured weekly in the chronically irradiated mice. The acute study data shows that topical treatment with estrogen did not alter UVB induced increases in hydrogen peroxide and PGE2. However topical estrogen treatment did appear to affect the infiltration of neutrophils into the skin following UVB exposure. This suggests that estrogen may play a role in modulating select inflammatory mediators when applied after UVB radiation. In the chronic study, there were no significant differences in the effects of estrogen in control or ovariectomized mice. However, estrogen treated mice developed more tumors of a higher grade compared to mice treated with Surgilube®. The results of this study suggest that estrogen may be increasing the severity of tumors through the inhibition of DNA repair as shown by the decreased levels of p53 in the skin surrounding tumors with increased levels of p53 in the actual tumors. Although the results of this study did not reach statistical significance, the clinical relevancy of developing more malignant versus benign neoplasms with topical estrogen treatment is important. Future studies are needed to investigate biological causes for the increased severity of neoplasms in SKH1 mice treated with topical estrogen. 2012-06-22 English text The Ohio State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=osu1337631752 http://rave.ohiolink.edu/etdc/view?acc_num=osu1337631752 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
| collection |
NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
Biomedical Research UVB skin cancer estrogen SKH1 |
| spellingShingle |
Biomedical Research UVB skin cancer estrogen SKH1 Creamer, Michelle UVB Exposure and Topical Estrogen Effects on the Development of Skin Cancer in a Pre- and Post-Menopausal Mouse Model |
| author |
Creamer, Michelle |
| author_facet |
Creamer, Michelle |
| author_sort |
Creamer, Michelle |
| title |
UVB Exposure and Topical Estrogen Effects on the Development of Skin Cancer in a Pre- and Post-Menopausal Mouse Model |
| title_short |
UVB Exposure and Topical Estrogen Effects on the Development of Skin Cancer in a Pre- and Post-Menopausal Mouse Model |
| title_full |
UVB Exposure and Topical Estrogen Effects on the Development of Skin Cancer in a Pre- and Post-Menopausal Mouse Model |
| title_fullStr |
UVB Exposure and Topical Estrogen Effects on the Development of Skin Cancer in a Pre- and Post-Menopausal Mouse Model |
| title_full_unstemmed |
UVB Exposure and Topical Estrogen Effects on the Development of Skin Cancer in a Pre- and Post-Menopausal Mouse Model |
| title_sort |
uvb exposure and topical estrogen effects on the development of skin cancer in a pre- and post-menopausal mouse model |
| publisher |
The Ohio State University / OhioLINK |
| publishDate |
2012 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=osu1337631752 |
| work_keys_str_mv |
AT creamermichelle uvbexposureandtopicalestrogeneffectsonthedevelopmentofskincancerinapreandpostmenopausalmousemodel |
| _version_ |
1719430616389255168 |