NOVEL ANTIMUTAGENIC COMPOUNDS

我们承担了一项关于小说自然而然的研究 抗突变药物。抗诱变剂是单独的化学物质 减少自发性或伤害性的化合物- 在完整的细胞群体中诱导突变。这项建议是为了 用短期试验来筛选；用生物测定法进行分离 定向方法学；通过光谱学确定化学结构 和湿化学方法学；测定结构-活性 通过系统的合成和化学变换的关系； 探索其生物学特性；探索其分子生物学特性 天然来源的新型抗突变药物的作用机制。这个 长期目标是制造潜在的化学预防药物 防止基因损伤，也许还有癌症。 使用一种专门为此目的开发的生物测定，甘草 光皮草，一种自古以来就被人类用来 它的调味和药用特性，被证明是 可复制的活跃的。活性存在于酚类化合物中。 级分和经色谱分离后的黄烷类化合物 此外，还发现了光滑素和光滑素。 成为有效的成分。产生这些的生物化验 这项试验研究的成功结果是基于众所周知的 Ames短期沙门氏菌致突变试验，但通过 使用烷化剂(甲烷磺酸乙酯)来诱导 突变。 基于这一成功，建议使用屏幕，与 也包括其他诱变治疗，以筛选 有关天然抗突变物质的其他例子 并对其活性成分进行鉴定。一项计划 建议在进行化学修饰的同时进行生物测试，以便 系统地探讨结构与结构之间的关系 以及这些小说系列中的活跃性。 除了对诱变现象的洞察和 其他被认为具有致突变性的生物领域 重要作用(衰老、遗传、致癌性、 环境问题)这些化合物可能在 人类预防性医学。

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.