Bioactivation and Covalent Binding of Halothane to Liver Macromolecules

The interaction of DNA with halothane or its metabolites was studied. Three methods were used in the study: incubation with isolated hepatocytes, liver microsomal incubations, and in vivo administration. Treatments (such as microsomal enzyme induction and hypoxia) known to enhance covalent binding of halothane to lipids and protein were used to create more favorable conditions for bioactivation. Using carbon-14 halothane, significant binding to liver proteins and phospholipids was reported, especially under hypoxic conditions. When halothane was administered in vivo or added to microsomal incubations or isolated liver cells, no binding of halothane to DNA or RNA was observed. (4 graphs, 41references, 3 tables)