DITERPENES AS INHIBITORS OF CARCINOGENESIS

谷胱甘肽-S-转移酶系统可广泛解毒 异种生物化合物，包括化学致癌物。青咖啡豆 诱导这个酶系统的活性显著增加。烘焙咖啡 豆类也有类似的诱导作用。速溶咖啡大约是 威力只有一半。对青咖啡豆的分级生产了六种 活性分数。从一种馏分中分离出卡维醇棕榈酸酯和咖啡醇 棕榈酸酯是两种二萜酸酯，已被分离和鉴定。这个 两种化合物约占诱导活性的40%。 发生在这些豆子里。本提案的一个目标是 分离和鉴定剩余的咖啡成分 提高谷胱甘肽S转移酶活性。在与这两家公司的进一步合作中 已经分离的化合物，我们建议研究结构活性 确定Kahweol和Cafestol结构特征的关系 棕榈酸酯决定了它们诱导GSH升高的能力 S-转移酶活性。两种二萜酯和其他化合物的作用 咖啡豆中谷胱甘肽S转移酶诱导化合物的研究 代谢致癌物质的额外的酶系统。的影响 这些化合物对致癌物诱发肿瘤的作用也将被研究。 其他工作将旨在开发敏感的技术，以 咖啡豆、速溶咖啡和咖啡中去污酯的定量 所消费的咖啡饮料。将进行类似的研究， 其他咖啡成分可诱导谷胱甘肽S转移酶升高 活动。所获得的数据将为评估 这些化合物在咖啡中食用时的潜在影响 饮料。到目前为止鉴定的两种二萜酯不同于任何 先前显示的化合物可诱导谷胱甘肽S转移酶活性增加。 二萜类化合物是植物中常见的成分。这种广为流传 分配加强了确定以下容量的重要性 抑制肿瘤的这类化合物的成员。

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.