SummaryThe mutagenicity of 1,2-dibromoethane (EDB) to Escherichia coli was reduced by the UV lightinduced excision repair system but unaffected by the loss of a major apurinic/apyrimidinic site repair function. At high doses, 70-90% of the EDB-induced mutations were independent of SOS-mutagenic processing and approximately 50% were independent of glutathione conjugation. The SOSindependent mutations induced by EDB were unaffected by the enzymes that repair alkylationinduced DNA lesions. EDB-induced base substitutions were dominated by GC to AT and AT to GC transitions. These results suggest that EDB-induced premutagenic lesions have some, but not all, of the characteristics of simple alkyl lesions. KeywordsDibromoethane; EDB; Escherichia coil; Miscoding lesions; DNA repair 1,2-Dibromoethane (EDB or DBE; has been used as an antiknock additive in leaded gasoline, an industrial solvent, a pesticide, and a food disinfectant (NIOSH, 1977). It is one of a class of potentially hazardous compounds, the haloalkanes, that has become widely distributed in the environment . EDB is highly toxic, causing liver and kidney necrosis and reproductive abnormalities (reviews Shih and Hill, 1981;Rannug, 1980;Ter Haar, 1980). It has been repeatedly shown to be carcinogenic to rodents, resulting in tumors in a number of organs, including the forestomach, liver, spleen and thyroid (NCI, 1978). Thus environmental exposure to EDB is a potential health hazard.The mutagenicity of EDB has been demonstrated in a number of genetic systems, including bacteria, yeast and other fungi, plants, insects, mammals and human cells (reviews, Fabricant and Chalmers, 1980;Rannug, 1980). Although EDB is a direct-acting mutagen in the Salmonella/microsome assay (McCann et al., 1975a), its mutagenicity has been shown to be further enhanced by metabolic activation (Rannug, 1980). Metabolic activation of EDB to its ultimate mutagenic and carcinogenic form has been hypothesized to occur by two different (Rannug, 1980; Anders and Livesey, 1980). One, mediated by the mixed-function oxygenases of liver microsomes, would yield bromoacetaldehyde and 2-bromoethanol as potential DNA-damaging agents (Hill et al., 1978;Banerjee et al., 1979). The other pathway, conjugation with glutathione mediated by enzymes present in liver cytosol, would yield as reactive products a half-sulfur-mustard or an episulfonium ion (Rannug, 1980;van Bladeren et al., 1980). The binding of EDB to DNA in vitro has been shown to be dependent on glutathione conjugation, and an S- [2-(N 7 -guanyl)ethyl]glutathione adduct has been identified (Ozawa and Guengerich, 1983;Inskeep and Guengerich, 1984). However, bromoacetaldehyde is a metabolite of EDB (Hill et al., 1978) and can bind to DNA without enzymatic activation (Banerjee et al., 1979). Both 2-bromoethanol and chloroacetaldehyde are bacterial mutagens (McCann et al., 1975b;Rannug et al., 1976;Rosenkranz, 1977), but bromoacetaldehyde is not, possibly due to its extreme toxicity (Rosenkranz, 1977). Thus, the identity of the genotoxic metabol...