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.