DITERPENES AS INHIBITORS OF CARCINOGENESIS

谷胱甘肽（GSH）S-转移酶系统可以解毒广泛的 异生化合物，包括化学致癌物。 绿色咖啡豆 诱导该酶系统活性显著增加。 烘焙咖啡 豆类也有类似的诱导作用。 速溶咖啡大约是 一半的力量。 绿色咖啡豆的分级已经产生了六种 活性组分 从一个馏分中，棕榈酸卡威酯和棕榈酸甘油酯 棕榈酸酯是两种二萜酯，已被分离和鉴定。 的 两种化合物约占诱导活性的40 发生在这些豆子上。 本建议的一个目标是 分离并鉴定剩余的咖啡成分， GSH S-转移酶活性增加。 在与两人的进一步合作中， 化合物已经分离，我们建议研究结构活性 关系，以确定kahweol的结构特征和 棕榈酸酯，决定其诱导GSH增加的能力 S-转移酶活性。 两种二萜酯和其他化合物的作用 咖啡豆中的谷胱甘肽S-转移酶诱导化合物将在 代谢致癌物质的额外酶系统。 的影响 还将研究这些化合物对致癌物诱导的瘤形成的作用。 更多的工作将旨在开发敏感技术， 定量咖啡豆、速溶咖啡和 咖啡饮料消费。 将进行比较研究， 发现其他咖啡成分可诱导GSH S-转移酶增加 活动 所获得的数据将为评估 这些化合物在咖啡中消耗时的潜在影响 饮料. 迄今为止鉴定的两种二萜酯与任何 先前显示的化合物诱导GSH S-转移酶活性增加。 二萜类化合物是植物中普遍存在的化学成分。 这种广泛 分配加强了确定能力的重要性， 这类化合物的成员抑制瘤形成。

The glutathione (GSH) S-transferase system can detoxifiy a wide range of xenobiotic compounds, including chemical carcinogens. Green coffee beans induce a marked increase in activity of this enzyme system. Roasted coffee beans have a comparable inducing effect. Instant coffee is approximately half as potent. Fractionation of green coffee beans has produced six active fractions. From one fraction, kahweol palmitate and cafestol palmitate, two diterpene esters, have been isolated and identified. The two compounds account for approximately 40% of the inducing activity occurring in these beans. One objective of the present proposal is to isolate and identify the remaining coffee constituents that induce increased GSH S-transferase activity. In further work with the two compounds already isolated, we propose to study structure-activity relationships to ascertain the structural features of kahweol and cafestol palmitates that determine their capacities to induce increased GSH S-transferase activity. The effects of the two diterpene esters and other GSH S-transferase-inducing compounds in coffee beans will be studied on additional enzyme systems that metabolize carcinogens. The effects of these compounds on carcinogen-induced neoplasia also will be investigated. Additional work will be aimed at developing sensitive techniques for quantitating the deterpene esters in coffee beans, instant coffee and coffee beverages as consumed. Comparable studies will be carried out with other coffee constituents found to induce increased GSH S-transferase activity. The data obtained will provide a basis for evaluating the potential impact of these compounds as they are consumed in coffee beverages. The two diterpene esters identified thus far are unlike any compounds previously shown to induce increased GSH S-transferase activity. Diterpenes are commonly occurrring constituents of plants. This widespread distribution enhances the importance of ascertaining the capacities of members of this class of compounds to inhibit neoplasia.