Ellagic acid embryoprotection in vitro: distribution and effects on DNA adduct formation. Teratology 1993 Apr;47(4):275-80
Date
04/01/1993Pubmed ID
8322221DOI
10.1002/tera.1420470404Scopus ID
2-s2.0-0027340086 (requires institutional sign-in at Scopus site) 2 CitationsAbstract
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)
Author List
Frank AA, Collier JM, Forsyth CS, Zeng W, Stoner GDMESH terms used to index this publication - Major topics in bold
Abnormalities, Drug-InducedAnimals
DNA Damage
Ellagic Acid
Embryo, Mammalian
Guanine
Methylnitrosourea
Organ Culture Techniques
Rats
Rats, Sprague-Dawley
Solubility
Teratogens
Yolk Sac
