RESUMO
The mutagenic properties of 1,2-dibromoethane (DBE) were studied in the Ames Salmonella typhimurium assay using the strains TA 1535 and TA 100. Kidney S9 fraction alone did not modify the direct mutagenic activity of DBE; but an addition of kidney S9 to liver S9 fraction yielded a higher mutagenic activity of DBE than with liver S9 fraction alone. Moreover, the addition of glutathione (GSH) to kidney S9 increased the mutagenic activity of DBE. Methimazole, a competitive inhibitor of the flavin-containing monooxygenase, reduced mutagenic activity suggesting that this enzyme may contribute to renal damage from DBE. No mutagens could be detected in the urine of rats treated with DBE.
Assuntos
Dibrometo de Etileno/toxicidade , Rim/metabolismo , Fígado/metabolismo , Mutagênicos/toxicidade , Animais , Fracionamento Químico , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Dibrometo de Etileno/administração & dosagem , Dibrometo de Etileno/urina , Glutationa/toxicidade , Injeções Intraperitoneais , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Metimazol/farmacologia , Testes de Mutagenicidade , Mutagênicos/administração & dosagem , Ratos , Ratos Wistar , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genéticaRESUMO
Metabolic disposition of ethylene oxide, dibromoethane, and acrylonitrile in rats after acute exposure was studied by examining the relationship between dose and urinary metabolites, and by establishing the influence of a glutathione precursor, L-2-oxothiazolidine-4-carboxylic acid (OTCA), on the above relationship. Respective urinary metabolites, hydroxyethylmercapturic acid, cyanoethylmercapturic acid, thiocyanate, and ethylene glycol, were quantified to estimate the extent to which each compound was metabolized. The animals were given either ethylene oxide (0.34, 0.68, or 1.36 mmol/kg), dibromoethane (0.2, 0.4, or 0.6 mmol/kg), or acrylonitrile (0.10, 0.38, or 0.76 mmol/kg). Urine samples were collected at 24 h. The metabolic biotransformation of all three chemicals to their respective mercapturic acids was strongly indicative of saturable metabolism. Administration of OCTA (4-5 mmol/kg) enhanced gluthathione availability and increased excretion of urinary mercapturic acids at the higher doses of the chemicals. This study indicates that OTCA increases the capacity for detoxification via the glutathione pathway thereby partially correcting the nonlinearity between the administered dose of ethylene oxide, dibromoethane, and acrylonitrile and the amount of certain urinary metabolites.