Increased mutagenicity of 1,2-dibromo-3-chloropropane and tris(2,3-dibromopropyl)phosphate in Salmonella TA100 expressing human glutathione S-transferases

• Published in: Carcinogenesis (New York) Vol. 14; no. 11; p. 2303
• Main Authors: Simula, T P, Glancey, M J, Söderlund, E J, Dybing, E, Wolf, C R
• Format: Journal Article
• Language: English
• Published: England 01-11-1993
• Subjects: Animals; Biotransformation; Dose-Response Relationship, Drug; Flame Retardants - toxicity; Gene Expression; Glutathione Transferase - biosynthesis; Glutathione Transferase - metabolism; Humans; Insecticides - toxicity; Microsomes, Liver - metabolism; Mutagenicity Tests; Mutagens - toxicity; Organophosphates - toxicity; Propane - analogs & derivatives; Propane - toxicity; Rats; Recombinant Proteins - biosynthesis; Recombinant Proteins - metabolism; Salmonella typhimurium - drug effects; Salmonella typhimurium - enzymology
• ISSN: 0143-3334
• DOI: 10.1093/carcin/14.11.2303

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.