| Abstrakt: |
1,2-Dibromo-[1,2-C]ethane was bound irreversibly to DNA when glutathione S-transferase or rat liver cytosolic components were added to incubations of calf thymus DNA and glutathione at 37°C. There was no DNA binding of 1,2-dibromoethane when glutathione was absent or in incubations of DNA with microsomal proteins with or without NADPH, thus supporting the proposal that the major route of DNA binding by 1,2-dibromoethane occurs via conjugation to glutathione. binding of 1,2-dibromoethane occurred most effectively when the YaYc (or ‘B’) isozyme of glutathione S-transferase was included in incubations of DNA with 1,2-dibromoethane and glutathione. Other dihaloalkanes were incubated with DNA in the presence of glutathione S-transferase and [S]glutathione. Of these, only 1,2-dibromo-3-chloropropane and tris-(2,3-dibromopropyl)-phosphate led to significant DNA binding of [S]glutathione. 1,2-dibromo-3-chloro-[1,3-C]propane was bound to DNA when glutathione and glutathione S-transferase were present. However, even higher 1,2-dibromo-3-chloropropane binding to DNA occurred when cytosol or microsomes were included in incubations without glutathione. When glutathione was added to incubations containing cytosol and 1,2-dibromo-3-chloropropane, total DNA binding was decreased. Thus, the actual amount of DNA binding by dihaloethanes may be the result of a complicated balance among the opposing roles of glutathione conjugation in detoxicating and activating processes. [ABSTRACT FROM PUBLISHER] |
