Rat hepatic glutathione S-transferase-mediated embryotoxic bioactivation of ethylene dibromide.
The embryotoxic effects of ethylene dibromide (EDB) bioactivation, mediated by purified rat liver glutathione S-transferases (GST), were investigated using rat embryos in culture. Significant EDB metabolism was observed with rat liver GST purified by affinity chromatography (specific activity of 188 +/- 11.3 nmol/min/mg protein). The reaction was enzymatic in nature and the conjugation rate was proportional to the concentration of EDB (up to 0.75 mM) and the enzyme present in the reaction medium. EDB activation by 100 units (1 unit = 1 nmol of glutathione consumed per min) of purified rat liver GST caused a significant reduction in general development as measured by crown-rump length, yolk sac diameter, somite number, and the composite score for different morphological parameters (Brown and Fabro methodology). Structures most significantly affected were the central nervous and olfactory systems as well as the yolk sac circulation and allantois. The results of this study clearly indicate that under in vitro conditions, bioactivation of EDB by GST can lead to embryotoxicity.
Mitra
A
A
Florida Toxicology Research Center, College of Public Health, University of South Florida, Tampa 33612.
Hilbelink
D R
DR
Dwornik
J J
JJ
Kulkarni
A
A
D000818:Animals; D001711:Biotransformation; D046508:Culture Techniques; D004622:Embryo, Mammalian / Q000187:drug effects* / Q000378:metabolism; D005314:Embryonic and Fetal Development / Q000187:drug effects; D015946:Ethylene Dibromide / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D005982:Glutathione Transferase / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D015946:Ethylene Dibromide; D005982:Glutathione Transferase