D. L. Hill, T. Shih, T. Johnston
Aug 1, 1978
Citations
1
Influential Citations
123
Citations
Quality indicators
Journal
Cancer research
Abstract
Abstract Biochemical investigations relating to mechanisms of action, activation, and inactivation have been made on the carcinogen, 1,2-dibromoethane. Measurable amounts of radioactivity from [1,2- 14 C]-1,2-dibromoethane became bound to protein, RNA, and DNA of all major tissues of rats. For each of these classes of macromolecules, the largest amounts of bound radioactivity were in the liver and kidneys. Optimum conditions for the rat liver glutathione S -transferase that utilizes 1,2-dibromoethane as a substrate have been established. The pH optimum was 8.2, the K m for 1,2-dibromoethane was 25 mm, and the V max was 2.1 µmol/min/g liver. Considerable enzyme activity was found in rat kidney; detectable activity was present in lung, testis, spleen, and heart. Enzymatic activity leading to the irreversible binding of radioactivity from [ 14 C]-1,2-dibromoethane to proteins in the reaction system was present in rat liver microsomes. The activity was inducible by phenobarbital but not by benz[ a ]anthracene. Reduced nicotinamide adenine dinucleotide phosphate was required for activity of both the noninduced and the induced reactions; MgCl 2 stimulated both reactions. Bromoacetaldehyde, a reactive compound probably involved in the irreversible binding, was identified as a metabolite formed in the reaction system. Radioactivity from [ 14 C]-1,2-dibromoethane also became bound to microsomal proteins by a nonenzymatic chemical reaction. The enzymatic reaction leading to binding to macromolecules and/or the chemical binding reaction may be involved in the biological activity of 1,2-dibromoethane.