PLACENTAL GLUTATHIONE-S-TRANSFERASE (GST-P) INDUCTION AS A POTENTIAL MECHANISM FOR THE ANTICARCINOGENIC EFFECT OF THE COFFEE-SPECIFIC COMPONENTS CAFESTOL AND KAHWEOL

The coffee specific diterpenes cafestol and kahweol (C+K) have been re ported to be anti-carcinogenic in several animal models, It has been p ostulated that this activity may be related to their ability to induce glutathione S-transferases (GSTs). We investigated the influence of a mixture of C+K, incorporated at various levels in the diet of Sprague -Dawley rats, on the expression of different hepatic GST iso-enzymes. Liver samples were examined using isoform-specific GST substrates and antibodies, and highly selective oligomers were employed to determine effects at the RNA level. A dose-dependent increase in general GST act ivity was observed in male and female animals following 28 or 90 days of treatment. A time-course study demonstrated that the maximal effect was observed within 5 days of treatment, Little or no effect was foun d on the activity of GST alpha and mu iso-enzymes, The most striking o bservation was a dose-dependent induction of placental glutathione S-t ransferase (GST-P) which could be demonstrated at the mRNA, protein an d enzymatic levels, This effect was observed in both male and female r ats, The maximal induction was attained within 5 days of treatment wit h C+K, remained elevated with continued treatment, but was reversible on withdrawal of treatment. Immunohistochemical examination of liver s lices revealed a strong even distribution of GST-P expression througho ut the acinus at the highest dose of C+K, while at lower doses the ind uction of GST-P occurred predominantly in periportal hepatocytes. Ther e was no indication of the presence of preneoplastic foci and, further more, the effect of C+K on the GST-P was completely reversible, These findings indicate that the anticarcinogenic mechanism of C+K may invol ve a specific induction of GST-P and suggest a potential role for GST- P in detoxifying carcinogenic compounds.