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.