CRUCIFERAE AND CARCINOGENESIS

十字花科植物和致癌作用

• 批准号: 3176192
• 负责人: EDWARD BRESNICK
• 金额: $ 22.23万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-08-01 至 1987-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3176192
• 关键词: Cruciferae; Leguminoseae; benzanthracenes; benzopyrenes; cancer prevention; carcinogenesis inhibitor; chemical carcinogen; chemical carcinogenesis; chemical structure function; flavonoids; high performance liquid chromatography; histology; indoles; isothiocyanates; lung neoplasms; medicinal plants; metaplasia; methylhydrazines; mutagen testing; neoplasm /cancer nutrition therapy; neoplasm /cancer pharmacology; nitrosourea; nutrition related tag; pancreas neoplasms; phorbols; plant extracts; skin neoplasms; tumor promoters

A group of chemists, biochemists and pathologists, most with a long-standing involvement in chemical carcinogenesis studies, have addressed the question of isolation and action of chemopreventive agents from the cabbage and pea. The isolation procedure will be monitored by short-term assays for anti-genotoxic and anti-promoter activities, including: (a) anti-mutagenesis in the Ames assay with benzo(a)pyrene [B(a)P] in the presence of rat liver S9 as the activating system, with 3,3 feet, 5,5 feet-tetramethylbenzidine in the presence of a ram seminal vesicle preparation (prostaglandin synthesizing system) as the activating system, and with two direct-acting substances, methylnitrosourea and methylmethane sulfonate; (b) anti-mutagenesis in a V79-hepatocyte cocultivation assay system in the presence of a nitrosamine derivative and a direct-acting mutagen; (c) protection against site-specific DNA damage produced by treatment of the hamster with N-nitrosobis(oxopropyl)amine (BOP), which affects the pancreas, and by treatment of the rat with 1,2-dimethylhydrazine (DMH), which affects the colon; (d) anti-promoter activity in a tetradecanoylphorbol acetate (TPA)-treated SENCAR mouse with epidermal ornithine decarboxylase, [3H]-deoxythymidine incorporation into epidermal DNA (autoradiography), with epidermal PGE2 levels, and hyperplasia serving as monitoring systems; (e) anti-metaplasia produced in hamster tracheal explants by B(a)P; and (f) inhibition of the nitrosation reaction in vivo and in vitro. Partially purified substances that are promising in the above tests will then be assayed for their ability to inhibit skin tumorigenesis; in an initiation-promotion protocol with DMBA as the initiator and TPA as the promoter; DMH-induced rat colon carcinogenesis; BOP-induced hamster pancreas carcinogenesis, under an initiation-promotion protocol; and B(a)P-induced hamster lung carcinogenesis. The above procedures will allow isolation of cancer chemopreventive agents and their pharmacokinetics will be determined. In addition, we will assess the activity in the above systems of two flavonoids, robinetin and apigenin, of benzylisothiocyanate and of indole-3-carbinol. The goal of this phase of the proposed research is to better define the chemopreventive action of benzylisothiocyanate and indole-3-carbinol, to determine whether the two flavonoids have such property, and to determine the pharmacokinetics of these compounds.

一群化学家，生物化学家和病理学家，大多数都有一个 长期参与化学致癌研究， 解决了化学预防剂的分离和作用问题 从卷心菜和豌豆中分离出来 隔离程序将由以下人员监测： 抗遗传毒性和抗启动子活性的短期测定， 包括：（a）在用苯并（a）芘的艾姆斯试验中的抗诱变 [B（a）P]在大鼠肝S9作为活化系统存在下，以3，3 英尺，5，5英尺-四甲基联苯胺在存在公羊精液 作为活化剂的囊泡制剂（前列腺素合成系统 系统，并与两个直接作用的物质，甲基亚硝基脲和 甲磺酸甲酯;（B）V79-肝细胞中的抗诱变 在亚硝胺衍生物存在下的共培养测定系统，和 直接作用的诱变剂;（c）防止位点特异性DNA损伤 通过用N-亚硝基双（氧代丙基）胺处理仓鼠产生 (BOP)，其影响胰腺，并通过用 1，2-二甲基肼（DMH），其影响结肠;（d）抗启动子 在十四烷酰佛波醇乙酸酯（TPA）处理的SENCAR小鼠中的活性， 表皮鸟氨酸脱羧酶，[3 H]-脱氧胸苷掺入 表皮DNA（放射自显影），表皮PGE 2水平，和 作为监测系统的增生;（e）在 仓鼠气管外植体通过B（a）P;和（f）亚硝化的抑制 在体内和体外的反应。 部分纯化的物质， 在上述测试中有希望的，然后将分析他们的能力， 抑制皮肤肿瘤发生;在与DMBA启动-促进方案中 为起始剂，TPA为启动剂; DMH诱导的大鼠结肠 致癌作用; BOP诱导的仓鼠胰腺致癌作用， 启动-促进方案;和B（a）P-诱导仓鼠肺 致癌作用 上述程序将允许隔离癌症 将测定化学预防剂及其药代动力学。 在 此外，我们将评估上述两个系统中的活动， 异硫氰酸苄酯和 吲哚-3-甲醇 本阶段拟议研究的目标是 更好地定义异硫氰酸苄酯的化学预防作用， 吲哚-3-甲醇，以确定是否有这样的两个黄酮类化合物 性质，并确定这些化合物的药代动力学。