Carcinogenesis, Vol 18, 1617-1622, Copyright © 1997 by Oxford University Press
M McVean and DC Liebler
Ultraviolet B (UVB, 290-320 nm) exposure results in a variety of cellular
insults including induction of cyclobutane pyrimidine dimers in DNA.
Accumulation of these lesions can lead to mutations in critical genes and
contribute to the development of nonmelanoma skin cancer. Topically applied
alpha-tocopherol (vitamin E) has previously been shown to prevent the
induction of skin tumors in UVB irradiated female C3H/HeNTac mice. We
hypothesized that alpha-tocopherol, which absorbs strongly in the UVB, may
act as a sunscreen to prevent photodamage. To explore possible mechanisms
of photoprotection, we topically applied alpha-tocopherol dispersed in a
neutral cream vehicle to the dorsal epidermis of female C3H/HeNTac mice and
exposed them to 2.5 J/m2/s of UVB for 60 min. Immediately after exposure,
we analyzed thymine dimer levels in DNA by capillary gas chromatography
with electron capture detection. Epidermal DNA from mice receiving this UVB
dose contained 247 +/- 42 pmol thymine dimers/micromol thymine. Topical
application of alpha-tocopherol inhibited dimer formation in a
dose-dependent manner. A 1% alpha-tocopherol dispersion inhibited the
formation of thymine dimers to 43% of levels in vehicle controls. Several
vitamin E compounds, including alpha-tocopherol acetate, alpha-tocopherol
methyl ether, gamma-tocopherol, and delta-tocopherol also inhibited thymine
dimer formation, but were five- to ten-fold less potent than alpha-
tocopherol. A variety of commercially available sunscreens were also less
potent than alpha-tocopherol in their ability to reduce dimer formation.
These results suggest that DNA photoprotection is an important mechanism by
which topically applied alpha-tocopherol can inhibit UVB induced skin
cancer. Alpha-Tocopherol acetate, the most common form of vitamin E in
commercial skin care products, conferred less protection, perhaps due to
its lower absorptivity in the UVB. Our results further underscore the
importance of determining which forms of vitamin E can inhibit specific
lesions involved in photocarcinogenesis.
ARTICLES
Inhibition of UVB induced DNA photodamage in mouse epidermis by topically applied alpha-tocopherol
Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson 85721-0207, USA.
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