Covalent Binding of Four DDD Isomers in the Mouse Lung: Lack of Structure Specificity

Publisher Website
Google Scholar
Abstract
Previous studies have shown that o,p''-DDD is activated and covalently bound in the mouse lung. In order to examine the structure dependency of the selective lung binding, the 14C-labelled DDD isomers p,p''-DDD, m,p''-DDD and o,m''-DDD were injected intravenously into female C57B1 mice and covalent binding was measured. Autoradiography of solvent-extracted tape-sections showed that all isomers were selectively and covalently bound in the lung alveolar region. As determined by exhaustive extraction of homogenized tissue, maximal binding was observed 4 hr after injection, although the lung/liver concentration ratio increased for 12 days. Covalent protein binding was also observed in vitro, implying that the activation of DDD to a reactive metabolite takes place in the target organ. Since the aryl-chlorine substitution pattern did not change the selective lung binding, bioactivation of DDD may take place at the ethane side-chain.