Polymorphism in the glutathione conjugation activity of human erythrocytes towards ethylene dibromide and 1,2-epoxy-3-(p-nitrophenoxy)-propane
article
In this study a polymorphism in the conjugating activity of human erythrocyte cytosol towards the dihaloethane, ethylene dibromide (EDB; 1,2-dibromoethane) was found. Two out of 12 human erythrocyte cytosols did not catalyze the formation of glutathione (GSH) conjugates of [1,2-14C]EDB. Ten cytosols formed the S,S'-ethylenebis(GSH) conjugate at a rate ranging from 0.5 to 3.2 (mean 1.76 ± 0.95) pmol min-1 (mg protein)-1. The activity of the cytosols towards EDB was compared with the activity towards 1,2-epoxy-3-(p-nitrophenoxy)-propane (EPNP) and 1-chloro-2,4-dinitrobenzene (CDNB). The GSH conjugates formed from EDB, EPNP and CDNB were all quantified by HPLC. Every cytosol was active with the classical GST substrate CDNB (2.04 ± 0.74 nmol min-1 (mg protein)-1). The two samples not showing any detectable activity towards EDB were also inactive towards EPNP: The activity towards EDB correlated significantly with EPNP (r(s) = 0.90, P < 0.005; Spearman's rank correlation), but not with CDNB (r(s) = 0.36, P > 0.10). In the incubations with EPNP, the alpha-, mu-, and pi- class glutathione S-transferase (GST) inhibitor S-hexyl(GSH) was included, indicating that the class-theta GST is the principal GST class conjugating EDB in erythrocyte cytosol. The apparent polymorphism of GST-theta which has recently been recognized to be crucial for several mono- and dihalomethanes, will thus also have considerable implications for the risk assessment of EDB.
Chemicals/CAS: 1,2-epoxy-3-(p-nitrophenoxy)propane, 5255-75-4; Dinitrochlorobenzene, 97-00-7; Epoxy Compounds; Ethylene Dibromide, 106-93-4; Glutathione Transferase, EC 2.5.1.18; Glutathione, 70-18-8; Isoenzymes; Nitrophenols
Chemicals/CAS: 1,2-epoxy-3-(p-nitrophenoxy)propane, 5255-75-4; Dinitrochlorobenzene, 97-00-7; Epoxy Compounds; Ethylene Dibromide, 106-93-4; Glutathione Transferase, EC 2.5.1.18; Glutathione, 70-18-8; Isoenzymes; Nitrophenols
Topics
TNO Identifier
82427
ISSN
03044165
Source
Biochimica et Biophysica Acta, 1243(3), pp. 469-476.
Pages
469-476
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