Metabolism of 1,2-dibromoethane in the human fetal liver.
1. Toxicity of 1,2-dibromoethane requires bioactivation via glutathione S-transferase. Since this enzyme is undetectable in the fetus of several laboratory animal species during early gestation, in vitro studies were carried out with human fetal liver to assess potential fetotoxicity. 2. Glutathione S-transferase occurs abundantly in the human fetal liver cytosol and its titer is equal to or exceeds that found in adult human liver when estimated using 1-chloro-2,4-nitrobenzene as the second substrate. 3. Human fetal liver cytosolic glutathione S-transferase metabolized 1,2-dibromoethane with a high efficiency (mean +/- SD specific activity of 3.10 +/- 0.83 nmol/min/mg protein). This reaction was enzymatic in nature and the rate of conjugation was proportional to the concentration of reduced glutathione, 1,2-dibromoethane and the enzyme present in the reaction medium. 4. A significant bioactivation with a possibility of only limited detoxication via cytochrome P-450-dependent oxidation suggests that human fetus may be at greater risk from 1,2-dibromoethane toxicity than adult.
Kulkarni
A P
AP
Florida Toxicology Research Center, College of Public Health, University of South Florida, Tampa 33612.
Edwards
J
J
Richards
I S
IS
D001711:Biotransformation; D003600:Cytosol / Q000378:metabolism; D015946:Ethylene Dibromide / Q000378:metabolism / Q000493:pharmacokinetics*; D005333:Fetus / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000196:embryology / Q000378:metabolism*
D015946:Ethylene Dibromide; D005982:Glutathione Transferase; D005978:Glutathione