Photoprotective actions of vitamin E in mouse skin: Prevention of UVB-induced DNA photodamage
AuthorMcVean, Maralee, 1967-
AdvisorLiebler, Daniel C.
MetadataShow full item record
PublisherThe University of Arizona.
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
AbstractUltraviolet exposure causes epidermal damage including induction of cyclobutane pyrimidine dimers in DNA. Accumulation of these lesions has been associated with mutagenesis and probably contributes to development of nonmelanoma skin cancer. Topically applied α-tocopherol previously has been shown to prevent UVB induced damage and skin tumor induction in mice. Thus, α-tocopherol, which absorbs strongly in the UVB, may act as a sunscreen to prevent photodamage. This dissertation explored possible mechanisms of photoprotection exerted by α-tocopherol. The UVB dose penetrating the epidermis was measured by monitoring the formation of UV induced DNA photodamage. Thymine dimer levels in DNA were analyzed by capillary gas chromatography with electron capture detection. Topical application of α-tocopherol prior to UVB exposure afforded significant protection against thymine dimer formation in mouse epidermis. Other vitamin E compounds and sunscreen compounds were less potent than α-tocopherol in their ability to reduce dimer formation. Multiple factors such as UVB absorbance and penetration of compounds into the skin could affect the photoprotective abilities of these compounds. The log integrated absorbance in the UVB was highly related to inhibition of thymine dimer formation in vitro, but not in vivo, where tocopherol derivatives conferred superior protection against UVB induced DNA photodamage despite having lower UVB absorbances. α-Tocopherol conferred the greatest photoprotection. DMSO was used as the vehicle to enhance penetration of the sunscreening agents. DMSO markedly increased the ability of commercial sunscreen compounds to inhibit dimer formation, but only modestly increased the photoprotective ability of the tocopherol homologues, suggesting that the tocopherol compounds penetrate the skin well regardless of vehicle. Cellular uptake and distribution of tocopherols was measured in an in vitro system. α-Tocopherol rapidly associated with cultured mouse keratinocytes and was transferred to the nucleus of the cells. The time course of α-tocopherol uptake corresponded temporally with DNA photoprotection in these cells. δ-Tocopherol and γ-tocopherol also afforded protection against DNA photodamage. γ-Tocopherol was taken up with similar kinetics as α-tocopherol, whereas δ-tocopherol accumulated to a lesser extent. These studies contributed evidence for the photoprotective actions of α-tocopherol and provided a strong rationale for the use of α-tocopherol in sunscreen products.
Degree ProgramGraduate College
Pharmacology and Toxicology