INCREASED MUTAGENICITY OF 1,2-DIBROMO-3-CHLOROPROPANE AND TRIS(2,3-DIBROMOPROPYL)PHOSPHATE IN SALMONELLA TA100 EXPRESSING HUMAN GLUTATHIONES-TRANSFERASES

We have expressed human glutathione S-transferases GSTA1-1 and GSTP1-1 in Salmonella typhimurium TA100 in order to assess the ability of the se enzymes to modulate the mutagenicity of 1,2-dibromo-3-chloropropane (DBCP) and tris(2,3-dibromopropyl)phosphate (Tris-BP). Both compounds were mutagenic when activated by Aroclor-induced rat liver microsomes . However, when Aroclor-induced rat fiver microsomes were used togethe r with the GST-expressing strains the mutagenicity of both DBCP and Tr is-BP was markedly potentiated. Neither of the GST-expressing strains potentiated the mutagenicity in the absence of microsomes, indicating that cytochrome P450-mediated metabolism was a prerequisite for GST-me diated potentiation. With DBCP both isozymes had comparable effects on mutagenic frequency, although the highest dose of DBCP was toxic in s trains expressing GSTP1-1. In the case of Tris-BP, GSTP1-1 was much mo re active in potentiating the mutagenicity. These results indicate tha t human GSTs can play an important role in the activation of compounds such as DBCP and Tris-BP to mutagenic metabolites.