Glutathione S-transferase-mediated induction of GC → AT transitions by halomethanes in salmonella
✍ Scribed by David M. DeMarini; Melissa L. Shelton; Sarah H. Warren; Tracey M. Ross; Joong-Youn Shim; Ann M. Richard; Rex A. Pegram
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 78 KB
- Volume
- 30
- Category
- Article
- ISSN
- 0893-6692
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✦ Synopsis
Halomethanes are among the most common muta-all four halomethanes at the hisG46 allele by pergenic and carcinogenic disinfection by-products forming colony probe hybridizations of Ç100 represent in the volatile/semivolatile fraction of chlori-vertants induced by each compound. The majority nated drinking water. Recent studies have demon-(96-100%) of the mutations were GC r AT transistrated that the mutagenicity of dichloromethane tions, and 87 -100% of these were at the second (CH 2 Cl 2 ) and bromodichloromethane (BrCHCl 2 ) position of the CCC/GGG target. In contrast, only can be mediated by a theta-class glutathione S-15% of mutants induced by CH 2 Cl 2 were GC r AT transferase (GSTT1-1). These studies used strain transitions in the absence of the GSTT1-1 gene in RSJ100 of Salmonella, which is a derivative of the strain TA100 (a homologue of TA1535 containing base-substitution strain TA1535 (hisG46, rfa, the plasmid pKM101). The ability of GSTT1-1 to DuvrB), into which has been cloned the GSTT1-1 mediate the mutagenicity of these di-and trihalogene from rat. In the present report, we have ex-methanes and the induction of almost exclusively tended these studies by demonstrating that the muta-GC r AT transitions by these compounds suggest genicity of two additional brominated trihalometh-that these halomethanes are activated by similar anes, bromoform (CHBr 3 ) and chlorodibromometh-pathways in RSJ100, possibly through similar reacane (ClCHBr 2 ), are also mediated by GSTT1-1 in tive intermediates. The implications of these find-RSJ100. Using a Tedlar bag vaporization tech-ings are discussed in relation to previous experinique, the mutagenic potencies (revertants/ppm) mental work on the GST-mediated bioactivation of for these two compounds as well as the compounds dihalomethanes, which includes the possible fortested previously rank as follows: CHBr 3 É ClCHBr 2 mation of GSH intermediates and/or GSH-DNA ú BrCHCl 2 É CH 2 Cl 2 . To explore the mutational adducts. Environ. Mol. Mutagen. 30:440-447, mechanism, we determined the mutation spectra of 1997 ᭧ 1997 Wiley-Liss, Inc.