Evaluation of a Human 3-Dimensional Skin Tissue Reconstruct As a Model to Screen for Xenobiotic Toxicity
Public Deposited- Last Modified
- February 28, 2019
- Creator
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Watson, Scott
- Affiliation: Gillings School of Global Public Health, Department of Environmental Sciences and Engineering
- Abstract
- An accurate, reproducible, and affordable means to screen the increasing number of xenobiotics for toxic effects to the skin is imperative for accurate assessment of potential health risk. My goal was to investigate the effects of naphthalene in two three-dimensional (3D) human skin reconstruct models, a commercially available MatTek, EFT-400 model and our in-house grown JCB-110 model. These two reconstruct models were exposed to 1,250, 6,250, 12,500, or 31,250 nmol of naphthalene on exposure days 1, 3, and 5. Naphthalene and its metabolites were measured in tissue culture media using liquid chromatography-mass spectrometry with atmospheric pressure photoionization source. Naphthyl-keratin adducts were observed by immunohistochemistry using antibodies specific to 1-naphthyl and 2-napthyl modified keratin-1 and keratin-10 proteins. The results provide evidence that naphthalene was metabolized and sequestered within the epidermis and that penetration of naphthalene through the reconstructs was negligible. The JCB-110 reconstructs were cultured to contain melanocytes in addition to keratinocytes and fibroblasts while the EFT-400 only contained keratinocytes and fibroblasts. The addition of melanocytes in the JCB-110 model provide a more physiologically relevant model. The successful culturing of the reconstructs demonstrates the ability to produce a test system that is suitable for the screening of xenobiotics. This research will provide a means forward to evaluate and develop 3D human skin reconstruct models that are suitable for high-throughput screening of dermally administered xenobiotics.
- Date of publication
- May 2012
- DOI
- Resource type
- Rights statement
- In Copyright
- Advisor
- Bodnar, Wanda
- Mathews, James
- Nylander-French, Leena A.
- Degree
- Master of Science in Public Health
- Academic concentration
- Environmental Health Sciences
- Degree granting institution
- University of North Carolina at Chapel Hill
- Graduation year
- 2012
- Language
- Deposit record
- e00f1df6-6c31-41ba-867b-150d86a8c8cb
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