DITERPENES AS INHIBITORS OF CARCINOGENESIS

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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.