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Prevention of DNA photodamage by vitamin E compounds and sunscreens: Roles of ultraviolet absorbance and cellular uptake
Author(s) -
McVean Maralee,
Liebler Daniel C.
Publication year - 1999
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/(sici)1098-2744(199903)24:3<169::aid-mc3>3.0.co;2-a
Subject(s) - pyrimidine dimer , photoprotection , in vivo , incubation , dna damage , biochemistry , thymine , dimer , biology , ultraviolet light , vitamin e , tocopherol , in vitro , microbiology and biotechnology , dna , antioxidant , chemistry , photochemistry , organic chemistry , photosynthesis
Topical application of α‐tocopherol (αTH), the most prominent naturally occurring form of vitamin E, inhibits ultraviolet (UV) B–induced photocarcinogenesis and DNA photodamage in C3H mice in vivo. In this study, we compared αTH with other vitamin E compounds and with three commercial sunscreen compounds for their ability to inhibit DNA photodamage in C3H mouse skin in vivo. When applied in a 5% dispersion in a neutral cream vehicle, α‐tocopherol (αTH), γ‐tocopherol (γTH), and δ‐tocopherol (δTH) each produced a statistically significant inhibition of thymine dimer formation, whereas α‐tocopherol acetate (αTAc) and α‐tocopherol methyl ether (αTOMe) did not. Application of 5% dispersions of the commercial sunscreen agent octylmethoxycinnamate also inhibited dimer formation, whereas ethylhexyl salicylate and oxybenzone did not, despite their considerably greater UVB absorbances than αTH. To test the hypothesis that cellular uptake and distribution are necessary for optimal photoprotection by tocopherols, photoprotection was studied in mouse 308 keratinocyte cells in vitro. Preincubation of 308 cells with 1 μM αTH for at least 2 h before exposure to 2.5 J/m 2 /s UVB for 10 min significantly (P < 0.05) attenuated thymine dimer formation. Pre‐incubation with 1 μM γTH, δTH, αTAc, or αTOMe for 2 h did not inhibit thymine dimer formation significantly. Uptake of αTH was measured after incubation with 1 μM [ 2 H 3 ]αTH (d 3 ‐αTH) and resulted in a time‐dependent increase in αTH levels. Use of d 3 ‐αTH allowed separate, simultaneous measurement of added d 3 ‐αTH and unlabeled endogenous αTH by gas chromatography–mass spectrometry. Accumulation of 167 ± 62 pmol d 3 ‐αTH/mg protein was measured within 1 h in whole‐cell fractions. d 3 ‐αTH in the nuclear fraction reached levels of 15 ± 4 pmol d 3 ‐αTH/mg protein at 2 h. Accumulation of αTH in the whole cell and nuclei corresponded temporally with significant protection against DNA photodamage. The kinetics of accumulation of the three tocopherols in whole cells and in nuclei were similar. Although only αTH conferred significant protection compared with irradiated controls at 2 h, the differences between individual tocopherols were not statistically significant. This work suggests that incorporation of tocopherol compounds into sunscreen products confers protection against procarcinogenic DNA photodamage and that cellular uptake and distribution of tocopherol compounds is necessary for their optimal photoprotection. Mol. Carcinog. 24:169–176, 1999. © 1999 Wiley‐Liss, Inc.