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Glutathione S ‐transferase‐mediated induction of GC → AT transitions by halomethanes in salmonella
Author(s) -
DeMarini David M.,
Shelton Melissa L.,
Warren Sarah H.,
Ross Tracey M.,
Shim JoongYoun,
Richard Ann M.,
Pegram Rex A.
Publication year - 1997
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/(sici)1098-2280(1997)30:4<440::aid-em9>3.0.co;2-m
Subject(s) - chemistry , mutagen , bromoform , dichloromethane , salmonella , strain (injury) , gene , ames test , mutagenesis , mutation , carcinogen , genetics , biochemistry , organic chemistry , bacteria , chloroform , biology , anatomy , solvent
Halomethanes are among the most common mutagenic and carcinogenic disinfection by‐products present in the volatile/semivolatile fraction of chlorinated drinking water. Recent studies have demonstrated that the mutagenicity of dichloromethane (CH 2 Cl 2 ) and bromodichloromethane (BrCHCl 2 ) can be mediated by a theta‐class glutathione S ‐transferase (GSTT1‐1). These studies used strain RSJ100 of Salmonella, which is a derivative of the base‐substitution strain TA1535 ( hisG46 , rfa , δ uvrB ), into which has been cloned the GSTT1‐1gene from rat. In the present report, we have ex tended these studies by demonstrating that the mutagenicity of two additional brominated trihalomethanes, bromoform (CHBr 3 ) and chlorodibromomethane (ClCHBr 2 ), are also mediated by GSTT1‐1 in RSJ100. Using a Tedlar bag vaporization technique, the mutagenic potencies (revertants/ppm) for these two compounds as well as the compounds tested previously rank as follows: CHBr 3 ≈ ClCHBr 2 > BrCHCl 2 ≈ CH 2 Cl 2 . To explore the mutational mechanism, we determined the mutation spectra of all four halomethanes at the hisG46 allele by per forming colony probe hybridizations of ∼100 revertants induced by each compound. The majority (96–100%) of the mutations were GC → AT transitions, and 87–100% of these were at the second position of the CCC/GGG target. In contrast, only15% of mutants induced by CH 2 Cl 2 were GC → AT transitions in the absence of the GSTT1‐1 gene in strain TA100 (a homologue of TA1535 containing the plasmid pKM101). The ability of GSTT1‐1 to mediate the mutagenicity of these di‐ and trihalomethanes and the induction of almost exclusively GC → AT transitions by these compounds suggest that these halomethanes are activated by similar pathways in RSJ100, possibly through similar reactive intermediates. The implications of these findings are discussed in relation to previous experimental work on the GST‐mediated bioactivation of dihalomethanes, which includes the possible formation of GSH intermediates and/or GSH‐DNAadducts. Environ. Mol. Mutagen. 30:440–447, 1997 Published 1997 Wiley‐Liss, Inc. This article is a US Government work and as such, is in the public domain in the United States of America.