| 8242859 |
Simula TP, Glancey MJ, Soderlund EJ, Dybing E, Wolf CR: Increased mutagenicity of 1,2-dibromo-3-chloropropane and tris (2,3-dibromopropyl) phosphate in Salmonella TA100 expressing human glutathione S-transferases. Carcinogenesis. 1993 Nov;14(11):2303-7.
We have expressed human glutathione S-transferases GSTA1-1 and GSTP1-1 in Salmonella typhimurium TA100 in order to assess the ability of these 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 liver microsomes were used together with the GST-expressing strains the mutagenicity of both DBCP and Tris-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-mediated potentiation. With DBCP both isozymes had comparable effects on mutagenic frequency, although the highest dose of DBCP was toxic in strains expressing GSTP1-1. In the case of Tris-BP, GSTP1-1 was much more active in potentiating the mutagenicity. These results indicate that human GSTs can play an important role in the activation of compounds such as DBCP and Tris-BP to mutagenic metabolites. |
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