| ABSTRACT: |
|
Ellagic acid (EA), a plant phenol found in various fruits and nuts,
was examined for its ability to inhibit aflatoxin B1 (AFB1) mutagenesis in
strain TA 100 of Salmonella typhimurium. In the presence of rat liver S-9
microsomal preparation, EA (1.5 microgram/plate) inhibited the number of
mutations induced by AFB1 (0.5 microgram/plate) by 50%. EA at a dose of
1000 micrograms/plate inhibited the mutation frequency by greater than
90%. EA was also tested for its ability to inhibit the DNA binding and
adduct formation of AFB1 in cultured explants of rat trachea and human
tracheobronchus. Explants were incubated in medium containing EA at
concentrations of 10, 50 and 100 microM for 16 h followed by the addition
of 1 microM [3H]AFB1 and EA for 24 h. DNA was isolated by phenol
extraction and hydroxylapatite chromatography. EA caused a dose-dependent
inhibition in the covalent binding of AFB1 to the DNA of both the rat
trachea (9-57% inhibition) and human tracheobronchus (24-79% inhibition).
After acid hydrolysis of the isolated DNA, the AFB1-DNA adducts were
separated by h.p.l.c. In tissues from both species, the major AFB1- DNA
adducts were AFB1-N7-Gua [8,9-dihydro-8-(N7-guanyl)-9-hydroxyAFB1] and
AFB1-N7-FaPyr (major) [8,9-dihydro-8-
(2,6-diamino-4-oxo-3,4-dihydropyrimid-5-yl formamido)-9-hydroxyAFB1], and
the formation of these adducts was reduced by 28-76% in the presence of
EA. These data indicate that EA has the potential to act as a naturally
occurring inhibitor of AFB1-related respiratory damage in rats and in
humans. |