title: 1,2-Dibromo compounds. Their mutagenicity in Salmonella strains differing in glutathione content and their alkylating potential.
abstract: The mutagenic activities of several structurally related dibromo compounds were compared in Salmonella strains sensitive to base substitution mutagenesis (TA1535 and/or TA100) and in the glutathione (GSH)-deficient derivative TA100/NG-57, using a preincubation procedure. The compounds tested were 1,2-dibromoethane (DBE), 1,2-dibromopropane (DBP), 1,2-dibromo-1-phenylethane (DBPE) and model compounds for the half-mustards resulting from their conjugation with GSH, i.e. the N-acetyl-S-2-bromoalkyl-L-cysteine methyl esters SBE, SBP, and SBPE, respectively. The alkylating potential of all compounds was assayed with the 4-(p-nitrobenzyl)pyridine (NBP) alkylation test. Five of the compounds showed a good correlation between relative mutagenic activity in TA100 and electrophilic reactivity in the NBP-test, the order of decreasing potency being SBE greater than SBP greater than DBPE greater than DBP. SBPE displayed the highest reactivity in the NBP-test, but was devoid of mutagenic activity. The mutagenic activity of DBE was substantially decreased in the GSH-deficient strain TA100/NG-57 and could be restored by pretreating the cells with GSH. None of the other chemicals showed different mutagenic activities in TA100 and TA100/NG-57. From the results it can be concluded that 2-bromothioethers possess higher alkylating activities than the 1,2-dibromo compounds. Methyl substitution has a deactivating effect on the mutagenic activity. The results with the phenyl-substituted analogue, DBPE, show that a higher alkylating activity does not always lead to a higher mutagenic activity.
mesh_terms: D000477:Alkylating Agents; D006842:Hydrocarbons, Brominated / Q000494:pharmacology*; D009152:Mutagenicity Tests; D009153:Mutagens; D009154:Mutation; D012486:Salmonella typhimurium / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000477:Alkylating Agents; D006842:Hydrocarbons, Brominated; D009153:Mutagens