GLUTATHIONE-S-TRANSFERASE MEDIATED DETOXIFICATION AND BIOACTIVATION OF XENOBIOTICS DURING EARLY HUMAN-PREGNANCY

Glutathione S-transferase (GST) with activity towards CDNB as a substr ate from human intrauterine conceptal tissues (HICT) at 6-10 weeks of gestation was purified similar to 200-fold by GSH coupled Sepharose 4B affinity chromatography. The preparations of affinity purified HICT-G ST were used in all the experiments. There was no significant differen ce in specific activity of GST towards CDNB among 6-, 8- and 10-week-o ld HICT. GST specific activity decreased with an increase in the gesta tional age using p-nitrobenzyl chloride and 3,4-dichloro-1-nitrobenzen e as the second substrate. Similarly, the lower the gestational age, t he higher was the degree of GST mediated ethylene dibromide (EDB) conj ugation with GSH. Covalent binding of [C-14]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 signifi cant amount of GST capable of detoxification or activation of xenobiot ics during the critical organogenesis period.