Epidemiological and animal studies linking high fruit and vegetable consumption to lower
cancer risk have strengthened the belief that long-term administration of isolated naturally occurring dietary constituents could reduce the risk of
cancer. In recent years, metabolites derived from
phytoalexins, such as
glucoraphanin found in broccoli and other cruciferous vegetables (Brassicaceae), have gained much attention as potential
cancer chemopreventive agents. The protective effect of these
micronutrients is assumed to be due to the inhibition of Phase-I
carcinogen-bioactivating
enzymes and/or induction of Phase-II detoxifying
enzymes, an assumption that still remains uncertain. The protective effect of
glucoraphanin is thought to be due to
sulforaphane, an
isothiocyanate metabolite produced from
glucoraphanin by
myrosinase. Here we show, in rat liver, that while
glucoraphanin slightly induces Phase-II
enzymes, it powerfully boosts Phase-I
enzymes, including activators of
polycyclic aromatic hydrocarbons (PAHs),
nitrosamines and
olefins. Induction of the
cytochrome P450 (CYP)
isoforms CYP1A1/2, CYP3A1/2 and
CYP2E1 was confirmed by Western immunoblotting. CYP induction was paralleled by an increase in the corresponding
mRNA levels. Concomitant with this Phase-I induction, we also found that
glucoraphanin generated large amount of various reactive radical species, as determined by electron paramagnetic resonance (EPR) spectrometry coupled to a radical-probe technique. This suggests that long-term uncontrolled administration of
glucoraphanin could actually pose a potential health hazard.