Assuntos
Glutationa Transferase/metabolismo , Glutationa/metabolismo , Fígado/enzimologia , Mitolactol/farmacologia , Mutagênicos , Mutação , Animais , Biotransformação , DNA/metabolismo , Escherichia coli/efeitos dos fármacos , Cinética , Microssomos Hepáticos/metabolismo , Mitolactol/metabolismo , Testes de Mutagenicidade , Ratos , Salmonella typhimurium/efeitos dos fármacosRESUMO
The influence of mammalian metabolizing enzymes on the mutagenic activity of dibromomethane and diiodomethane was investigated by using Salmonella typhimurium strain TA100 as indicator. The 2 compounds are known to be metabolized via an oxidative pathway catalysed by microsomal enzymes as well as through direct enzymatic conjugation with glutathione; both pathways possibly give rise to reactive electrophilic intermediates. In mutagenicity plate assays with pre-incubation, dibromo- and diiodo-methane were directly mutagenic towards strain TA100; their mutagenic activity was enhanced upon incubation either with rat-liver microsomes or with the cytosol fraction of the same organ, containing the glutathione S-transferases. These data can be taken as an indication that both microsomal oxidation and conjugation to glutathione are indeed responsible for the mammalian mutagenic activation of dihalomethanes.
