Glutathione S-transferase mediated detoxification and bioactivation of xenobiotics during early human pregnancy.
Glutathione S-transferase (GST) with activity towards CDNB as a substrate from human intrauterine conceptual tissues (HICT) at 6-10 weeks of gestation was purified approximately 200-fold by GSH coupled Sepharose 4B affinity chromatography. The preparations of affinity purified HICT-GST were used in all the experiments. There was no significant difference in specific activity of GST towards CDNB among 6-, 8- and 10-week-old HICT. GST specific activity decreased with an increase in the gestational age using p-nitrobenzyl chloride and 3,4-dichloro-1-nitrobenzene as the second substrate. Similarly, the lower the gestational age, the higher was the degree of GST mediated ethylene dibromide (EDB) conjugation with GSH. Covalent binding of [14C]EDB to DNA and protein was greater in the presence of HICT-GST at 6 weeks gestation than that at 10 weeks gestation. These results suggest that HICT possess a significant amount of GST capable of detoxification or activation of xenobiotics during the critical organogenesis period.
Datta
K
K
Florida Toxicology Research Center, College of Public Health, University of South Florida, Tampa 33612.
Roy
S K
SK
Mitra
A K
AK
Kulkarni
A P
AP
D004268:DNA-Binding Proteins; D015946:Ethylene Dibromide / Q000378:metabolism; D005260:Female; D005865:Gestational Age; D005982:Glutathione Transferase / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D008658:Inactivation, Metabolic; D009578:Nitrobenzenes / Q000378:metabolism; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D014599:Uterus / Q000201:enzymology; D015262:Xenobiotics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D009578:Nitrobenzenes; D015262:Xenobiotics; D015946:Ethylene Dibromide; C027562:4-nitrobenzyl chloride; D005982:Glutathione Transferase