| ABSTRACT: |
|
Ellagic acid (EA) is a naturally occurring plant phenol that was
recently demonstrated to protect cultured rat embryos from the embryotoxic
effects of N-methyl-N-nitrosourea (MNU). The teratogenic mechanism of
action of MNU, as well as other methylating agents, is debated: both cell
death and mutation have been proposed. In some model systems, EA has been
reported to selectively decrease the mutagenic DNA adduct O6-methylguanine
(O6MG) when compared to the cytotoxic DNA adduct N7-methylguanine (N7MG).
The present study was initiated to determine 1) the distribution of 14C-EA
and 3H-MNU in the rat whole embryo culture model system and 2) the effects
of EA on MNU-induced DNA adduct formation in this model system. 14C-EA (50
microM for 2 hr, known embryoprotective concentration; no MNU added) was
used to demonstrate access of EA to the embryo within the 2 hr exposure
period. The majority of EA (99.5%) remained in the media while tissue
concentrations of 57.0 and 47.9 pmol/mg were attained in the yolk sacs and
embryos, respectively. Similarly, MNU (75 microM for 1 hr, known effective
concentration; no EA added) was distributed between the media, yolk sacs,
and embryos at 99.7%, 73.7 and 112.9 pmol/mg, respectively. When
non-radiolabeled EA (50 microM for 2 hr) was used to protect embryos prior
to exposure to 3H-MNU (75 microM for 1 hr), the distribution of MNU in the
model system was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) |