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Covalent binding of [14C]benzene to cellular organelles and bone marrow nucleic acids

1981; Elsevier BV; Volume: 30; Issue: 10 Linguagem: Inglês

10.1016/0006-2952(81)90452-4

1873-2968

David P. Gill, Ahmed E. Ahmed,

Drug Transport and Resistance Mechanisms

Our objective was to determine whether reactive metabolites of benzene covalently bind to cellular proteins and nucleic acids of the hematopoietic organs and liver of the mouse. The distribution and binding of [14C]benzene after a single dose (880 mg/kg, s.c., 0.75 mCi/kg) were investigated at 3, 6, 12, and 24 hr. Maximum levels of radioactivity were found at 3 hr in liver, spleen, bone marrow, and blood. Maximum covalent binding occurred at 6 hr in liver, spleen, and bone marrow. Chemical fractionation of label derived from [14C]benzene indicated that 0.5, 7, and 17 per cent of the covalently bound label in liver, spleen, and bone marrow was recovered in the nucleic acids. Upon subcellular fractionation of liver, total radioactivity was localized chiefly in the cytosol (1723 dpm/mg protein) and mitochondria (1433 dpm/mg protein). Of the total radioactivity recovered in various organelles, mitochondria had the highest proportion covalently bound (25 per cent). These studies indicate that label derived from [14C]benzene covalently binds to nucleic acids of hematopoietic cells, the major site of toxicity. In addition, the high levels of covalent binding with macromolecules of the mitochondria suggest that their functions may be impaired by benzene.