| ABSTRACT: |
|
The effect of ellagic acid, a naturally occurring plant phenol, on the
binding to DNA and metabolism of benzo(a)pyrene (BP) and
trans-7,8-dihydro-7,8-dihydroxybenzo(a)pyrene (BP 7,8-DHD) in cultured
explants of strain A mouse lung was investigated. The explants were
cultured in a rocking organ culture chamber for 16 h in the presence or
absence of 10, 25, 50, and 100 microM ellagic acid. These concentrations
of ellagic acid were nontoxic as determined by biochemical and
histological methods. The ellagic acid was then removed from the cultures,
and the explants were incubated with either 1 microM [3H]BP or [3H]BP
7,8-DHD for 24 h. Explant DNA was isolated using hydroxylapatite
chromatography, and the BP metabolites in the medium were analyzed by
high-pressure liquid chromatography. Ellagic acid (50 microM) inhibited
the binding of BP and BP 7,8-DHD to lung DNA by 46 to 50% and 60 to 70%,
respectively. High-pressure liquid chromatography analysis showed that
ellagic acid (100 microM) inhibited the metabolism of BP by 20 to 40% and
of BP 7,8-DHD by 20%, as indicated by the increased amounts of
unmetabolized substrates and decreased amounts of metabolites in the
medium. The major BP:DNA adduct in the explants was 7R-N2-[10 beta-[7
beta, 8 beta, 9 alpha-trihydroxy-7,8,9,10-tetrahydrobenzo(a)pyrene]yl:
deoxyguanosine, and its formation was reduced by 60 to 65% in the presence
of 100 microM ellagic acid. These data suggest that the reduction of BP
and BP 7,8-DHD metabolite binding to DNA by ellagic acid may have been due
to inhibition of the formation and/or removal of BP 7,8-diol-9,10-epoxide
prior to its binding to DNA. |