NOVEL ANTIMUTAGENIC COMPOUNDS

我们对自然发生的小说进行了一项研究 抗突变剂。 抗诱变剂是单独的化学物质 减少自发或伤害数量的化合物- 在完整细胞群中诱导突变。 这个提议是为了 使用短期测试来筛选；通过生物测定法分离 定向方法；通过光谱确定化学结构 和湿化学方法；确定结构-活性 通过系统合成和化学转化建立关系； 探索生物特性；并探索分子 天然来源的新型抗诱变剂的作用机制。 的 长期目标是制造潜在的化学预防剂 对抗遗传损伤，或许还有癌症。 使用专门为此目的开发的生物测定法，甘草 glabra，一种众所周知的植物，自古以来就被人类用来 它的调味和药用特性，被证明是 可重复活跃。 该活性存在于酚类物质中 馏分和色谱分离后的黄酮类化合物 发现了光甘草烯以及少量的光甘草定和甘草醇 成为活性成分。 产生这些的生物测定 本试验研究的成功结果基于众所周知的 艾姆斯短期沙门氏菌致突变性测定，但经过修改 使用烷化剂（甲磺酸乙酯）诱导 突变。 基于这一成功，建议使用屏幕， 还包括其他诱变治疗，以筛选 相关天然抗突变物质的其他例子 植物并鉴定其活性成分。 一个程序 建议进行化学修饰并结合生物测试，以便 系统地探索结构之间的关系 这些小说系列中的活动。 除了对诱变现象和 据信致突变性发挥作用的其他生物领域 重要作用（衰老、遗传、致癌性、 环境问题）这些化合物可能具有一定的潜力 人类预防医学。

We have undertaken a study of novel naturally occuring antimutagenic agents. Antimutagens are individual chemical compounds that decrease the numbers of spontaneous or injury- induced mutations in intact cell populations. This proposal is to use short-term tests to screen for; isolate by use of bioassay directed methodology; determine chemical structure by spectroscopic and wet chemical methodology of; determine structure-activity relations by systematic syntheses and chemical transformations of; explore the biological properties of; and explore the molecular mechanisms of action of novel antimutagens of natural origin. The long-term objectives are to make potential chemopreventive agents against genetic damage and, perhaps, cancer. Using a bioassay specially developed for the purpose, Glycyrrhiza glabra, a well known plant used by humans since ancient times for its flavoring and medicinal properties, was shown to be reproducably active. The activity was present in the phenolic fractions and, after chromatographic resolution, the flavanoids glabrene and, to a lesser extent, glabridin and glabrol, were found to be the active constituents. The bioassay which produced these successful results in this trial study is based upon the well known Ames short-term Salmonella mutagenicity assay but modified through the use of an alkylating agent (ethyl methanesulfonate) to induce mutations. Based upon this success, it is proposed to use the screen, with the inclusion of other mutagenic treatments as well, to screen for additional examples of natural antimutagenic substances in related plants and to identify the active constituents. A program of chemical modification accompanied by biotesting is proposed so as to explore in a systematic way the relationship between structure and activity in these novel series. In addition to the insights into the mutagenic phenomenon and the other biological areas where mutagenicity is believed to play an important role (ageing, heredity, carcinogenicity, environmental concerns) these compounds may have some potential in preventive human medicine.