ANTITOXIDANT ACTIONS OF BETA-CAROTENE

β-胡萝卜素的抗氧化作用

• 批准号: 2097654
• 负责人: Daniel C Liebler
• 金额: $ 16.63万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-04-01 至 1996-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2097654
• 关键词: antioxidants; autooxidation; carcinogenesis inhibitor; carotene; free radical oxygen; gas chromatography; high performance liquid chromatography; hydrogen peroxide; laboratory rat; liposomes; neoplastic transformation; nuclear magnetic resonance spectroscopy; singlet oxygen; tissue /cell culture; ultraviolet spectrometry

Abundant evidence indicates that carotenoids, which are present in many fruits and vegetables, decrease the risk of some cancers in humans. The provitamin A carotenoid beta-carotene inhibits neoplastic development in several cellular and animal models of cancer, apparently by a mechanism that does not involve its conversion to vitamin A. beta-Carotene and other carotenoids are postulated to inhibit carcinogenesis by acting as antioxidants, which scavenge reactive free radicals, singlet oxygen and other oxidants involved in carcinogenic tissue injury. The overall objective of the proposed project is to test this "antioxidant hypothesis" by measuring antioxidant actions of beta-carotene in cell models where beta-carotene inhibits carcinogenesis. The initial objective of the project is to identify products formed by free radical scavenging and singlet oxygen quenching reactions of beta-carotene. Both chemically defined model systems and biological membrane systems will be used to identify beta-carotene oxidation products, which will be isolated by high performance liquid chromatography and characterized by UV-vis and NMR spectroscopy and mass spectrometry. A key goal of this work will be to distinguish products of beta-carotene antioxidant reactions, which consume beta-carotene and block radical chain reactions, from products of autoxidation reactions, which consume beta-carotene without blocking radical chain reactions. The validity of specific beta-carotene oxidation products as specific markers for beta-carotene antioxidant reactions will be tested in liposomes and biological membranes. Formation of putative antioxidant-specific marker products will be correlated with inhibition of specific biochemical markers for oxidative damage. Once the identities and applicability of antioxidant-specific marker products has been established, specific and sensitive high performance liquid chromatography, gas chromatography, or gas chromatography-mass spectrometry assays will be developed to measure product formation in biological samples. These studies then will be extended to C3H/10T1/2 and JB6 cell models for chemical carcinogenesis, in which carcinogen- and tumor promoter-induced neoplastic transformation in vitro is inhibited by beta-carotene or other antioxidants. beta-Carotene antioxidant reactions will be measured by analyzing marker products and correlating their formation with inhibition of oxidative cellular damage and transformation. The fundamental information generated by this projected about mechanisms of carotenoid anticarcinogenic actions can be applied to future investigations of cancer prevention in animals and humans.

大量证据表明，类胡萝卜素存在于许多 水果和蔬菜，降低了人类某些癌症的风险。 这 Provitamin A类胡萝卜素β-胡萝卜素抑制肿瘤发育 几种癌症的细胞和动物模型，显然是通过机制 这不涉及其转换为维生素A.β-胡萝卜素和其他 假设类胡萝卜素是通过作用为抑制癌变的 抗氧化剂，清除反应性自由基，单线氧和 其他参与致癌组织损伤的氧化剂。 总体 拟议项目的目的是检验这种“抗氧化假设” 通过测量β-胡萝卜素在细胞模型中的抗氧化作用 β-胡萝卜素抑制癌变。 最初的目标 项目是确定由自由基清除和 β-胡萝卜素的单线氧反应。 两者都在化学上 定义的模型系统和生物膜系统将用于 识别β-胡萝卜素氧化产物，将通过高 性能液相色谱法，以UV-VIS和NMR为特征 光谱和质谱法。 这项工作的关键目标是 区分β-胡萝卜素抗氧化剂反应的产物，该反应消耗 β-胡萝卜素和阻断自由基链反应，来自 自氧化反应，消耗β-胡萝卜素而不阻塞 自由基链反应。 特定β-胡萝卜素氧化的有效性 作为β-胡萝卜素抗氧化反应的特定标记的产品将 在脂质体和生物膜中进行测试。 推定的形成 抗氧化剂特异性标记产物将与抑制相关 氧化损伤的特定生化标记。 一旦身份和 已经建立了抗氧化剂特异性标记产品的适用性， 特定敏感的高性能液相色谱，气体 色谱法或气相色谱 - 质谱法测定将是 开发用于测量生物样品中的产品形成。 这些 然后，研究将扩展到C3H/10T1/2和JB6细胞模型 化学致癌作用，其中致癌物和肿瘤启动子诱导 β-胡萝卜素或其他的肿瘤转化在体外受到抑制 抗氧化剂。 β-胡萝卜素抗氧化反应将通过 分析标记产品并将其形成与抑制相关 氧化细胞损伤和转化。 基本 该预测产生的有关类胡萝卜素机制的信息 抗癌作用可以应用于癌症的未来研究 预防动物和人类。