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Protection
against UV-light-induced skin carcinogenesis in SKH-1 high-risk mice by
sulforaphane-containing broccoli sprout extracts.
Cancer Lett. 2005 Nov 2;
Dinkova-Kostova AT, Jenkins SN, Fahey JW, Ye L, Wehage SL, Liby KT, Stephenson
KK, Wade KL, Talalay P.
The Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Department of
Pharmacology and Molecular Sciences, School of Medicine, Johns Hopkins
University, 725 N. Wolfe Street, Baltimore, Maryland 21205, USA.
Aerobic life, UV solar radiation, genetic susceptibility, and immune status
contribute collectively to the development of human skin cancers. In addition to
direct DNA damage, UV radiation promotes the generation of reactive oxygen
intermediates that can cause oxidative damage and inflammation, and ultimately
lead to tumor formation. Treatment of murine and human keratinocytes with the
isothiocyanate sulforaphane elevated phase 2 enzymes and glutathione and
protected against oxidant toxicity. Topical application of
sulforaphane-containing broccoli sprouts extracts induced the phase 2 response
in mouse skin in vivo. Sulforaphane inhibited cytokine-dependent
(gamma-interferon or lipopolysaccharide) induction of iNOS in RAW 264.7
macrophages. The UV-radiation-induced skin carcinogenesis in 'initiated
high-risk mice' was substantially inhibited by broccoli sprout extracts
containing sulforaphane. After completion of the UV irradiation schedule
(30mJ/cm(2)/session twice a week for 20 weeks), groups of approximately 30 mice
were treated topically on their backs (5 days a week for 11 weeks) with broccoli
sprout extract containing either the equivalent to 0.3mumol (low dose) or
1.0mumol (high dose) sulforaphane, respectively. At this time point, the tumor
incidence had reached 100% in the control mice. Tumor burden, incidence, and
multiplicity were reduced by 50% in the animals that received the high dose of
protector. Tumor incidence and multiplicity did not differ between the low
dose-treated and the control groups, but the low dose treatment resulted in a
substantial reduction of the overall tumor burden. Thus, topical application
of sulforaphane-containing broccoli sprout extracts is a promising strategy for
protecting against skin tumor formation after exposure to UV radiation.
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