EFFECTS OF ANTICARCINOGENIC MONOTERPENES ON PHASE-II HEPATIC METABOLIZING ENZYMES

The monocyclic monoterpenoid compounds limonene and sobrerol have anti carcinogenic activity when fed during the initiation stage of dimethyl benz[a]anthracene (DMBA)-induced rat mammary carcinogenesis. Here we i nvestigated the potential roles of hepatic glutathione-S-transferase ( GST; EC 2.5.1.18) and uridine diphosphoglucuronosyl transferase (UDPGT ; EC 2.4.1.17) in monoterpene-mediated chemoprevention. Diets containi ng the isoeffective anticarcinogenic terpenes, 5% limonene or 1% sobre rol, elevated hepatic GST activity > 2-fold when measured using the ge neral substrate 1-chloro-2,4-dinitrobenzene and 3,4-dichloronitrobenze ne for the GST dimer 3-3. However, there were no significant changes i n hepatic GST activity when 1,2-epoxy-3-(p-nitrophenoxy)propane was us ed. We found that both terpene diets increased GST affinity-purified p rotein 1.5-fold and the HPLC subunit profile. Liver GST subunit 3 had the greatest increase followed by 1 and 4 with no change in subunit 2. Both terpene diets significantly increased the activity of the methyl cholanthrene-inducible and the phenobarbital-inducible UDPGT isozymes. We propose that much of the anticarcinogenic activity of these monocy clic monoterpenes during the initiation phase of DMBA carcinogenesis i s mediated through the induction of the hepatic detoxification enzymes GST and UDPGT.