The anticarcinogenic properties of broccoli are believed to be due to modification of detoxification
enzymes by a group of
isothiocyanates, hydrolysis products of
glucosinolates, particularly
sulforaphane. We previously showed that the
nitrile crambene (1-cyano-2-hydroxy-3-butene), present in most Brassica vegetables, induces hepatic
quinone reductase activity when administered to rats. In this study, we compared the effects of seven daily oral doses of
crambene (50 mg/kg rat/day) and
sulforaphane (50 mg/kg rat/day) on induction of hepatic
quinone reductase activity in Fischer 344 rats. The two treatments produced similar effects, with
crambene and
sulforaphane producing 1.5- and 1.7-fold induction in hepatic
quinone reductase activity, respectively. Additionally, we evaluated the effect of
crambene on
quinone reductase activity in Hepa 1c1c7 cells, because this system had been shown to possess high sensitivity to
sulforaphane and is commonly used for screening anticarcinogenic compounds.
Crambene (5 mM) induced
quinone reductase activity and caused cell cycle arrest in the G2/M phase in mouse Hepa 1c1c7 cells, rat H4IIEC3 cells, and human Hep G2 cells (> 95% viability). Doses of
crambene needed for induction of
quinone reductase in cell culture were approximately 100-fold greater than effective doses of
sulforaphane. These findings indicate that
hepatoma cell lines may not accurately reflect relative potency of
anticarcinogens in Fischer 344 rats.