Protection against UV-light-induced skin carcinogenesis in SKH-1 high-risk mice by sulforaphane-containing broccoli sprout extracts
Protection against UV-light-induced skin carcinogenesis in SKH-1 high-risk mice by sulforaphane-containing broccoli sprout extracts
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DOI：
10.1016/j.canlet.2005.09.012
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发表时间：
2006-08-28
期刊：
影响因子：
9.7
通讯作者：
Talalay, Paul
中科院分区：
文献类型：
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作者：
Dinkova-Kostova, Albena T.;Jenkins, Stephanie N.;Talalay, Paul
有氧生活，紫外线太阳辐射，遗传易感性和免疫状态共同促进人类皮肤癌的发展。除了直接的DNA损伤外，紫外线辐射还促进活性氧中间体的产生，这些中间体可引起氧化损伤和炎症，并最终导致肿瘤形成。用异硫氰酸萝卜硫素处理小鼠和人角质形成细胞可提高2相酶和谷胱甘肽，并保护其免受氧化剂毒性。局部应用含萝卜硫素的西兰花芽提取物在小鼠体内皮肤中诱导2相反应。莱菔硫烷抑制RAW 264.7巨噬细胞中iNOS的精氨酸依赖性（γ-干扰素或脂多糖）诱导。含有萝卜硫素的西兰花芽提取物基本上抑制了紫外线辐射诱导的皮肤癌发生。完成紫外线照射计划（30 mJ/cm（2）/次，每周两次，持续20周）后，用分别含有相当于0.3 μ mol（低剂量）或1.0 μ mol（高剂量）莱菔硫烷的西兰花芽提取物对每组30只小鼠的背部进行局部处理（每周5天，持续11周）。在该时间点，对照小鼠的肿瘤发生率已达到100%。在接受高剂量保护剂的动物中，肿瘤负荷、发病率和多样性降低了50%。低剂量给药组和对照组之间的肿瘤发生率和多样性无差异，但低剂量给药导致总体肿瘤负荷大幅降低。因此，局部应用含有萝卜硫素的西兰花芽提取物是一种有前途的策略，用于保护暴露于紫外线辐射后皮肤肿瘤的形成。(c)2005爱思唯尔爱尔兰有限公司保留所有权利。
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 (30 mJ/cm(2)/session twice a week for 20 weeks), groups of similar to 30 mice were treated topically on their backs (5 days a week for 11 weeks) with broccoli sprout extract containing either the equivalent to 0.3 mu mol (low dose) or 1.0 mu mol (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. (c) 2005 Elsevier Ireland Ltd. All rights reserved.