| ABSTRACT: |
|
Over 1500 structurally different chemicals have been identified with
potential cancer chemopreventive properties. These properties may be
studied by employing short-term tests which provide important mechanistic
data and preliminary assessment of the efficacy of these agents. We have
previously reported on the use of a cell-free system concomitant with DNA
adduct modulation to study more than 30 potential chemopreventive agents.
Here we describe the use of a human breast tumor epithelial cell line
(MCF-7) to study the effects of 7 chemopreventive agents,
N-acetylcysteine, benzylisocyanate, chlorophyllin, curcumin, ellagic acid,
genistein and oltipraz on dibenz[a,l]pyrene (DBP)-DNA adduction. Treatment
of MCF-7 cells with DBP (10 nM, 24 h) produced one predominant (60%)
dA-derived and at least five other dA- or dG-derived adducts (3242
adducts/10(9) N). Pretreatment of cells with oltipraz (15 uM) for 4, 8 or
16 h followed by treatment with DBP resulted in a diminished DNA adduction
by 51%, 58% and 78%, respectively. A dose-dependent decrease in DBP DNA
adduction by 12%, 32%, 70% and 95% was also observed upon pretreatment of
the cells for 20 h with 1.5 uM, 5 uM, 15 uM and 30 uM oltipraz,
respectively. Of the other 6 agents tested at 30 uM, chlorophyllin
substantially resulted in diminished DBP-DNA adduction (69%) while ellagic
acid and genistein were only moderately effective (44% each);
benzylisocyanate and N-acetylcysteine were ineffective and curcumin was
toxic at this dose. These data suggest that oltipraz and chlorophyllin
were highly effective, while genistein and ellagic acid were moderately
effective in diminishing DBP-DNA adduction in human breast epithelial
cells. |