Covalent binding of four DDD isomers in the mouse lung: lack of structure specificity.
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.
Lund
B O
BO
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Ghantous
H
H
Bergman
A
A
Brandt
I
I
D000818:Animals; D001345:Autoradiography; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003632:Dichlorodiphenyldichloroethane / Q000378:metabolism*; D007536:Isomerism; D008055:Lipids / Q000032:analysis; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D051379:Mice; D013329:Structure-Activity Relationship; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism
D008055:Lipids; D003632:Dichlorodiphenyldichloroethane