Covalent binding of reactive intermediates to hemoglobin in the mouse as an approach to studying the metabolic pathways of 1,2-dichloroethane.
CBA mice were given 14C-labelled 1,2-dichloroethane by intraperitoneal injection. Metabolic pathways leading to the formation of electrophilic intermediates were studied through the determination, by ion-exchange chromatography, of the products of reaction of this labelled substrate with nucleophilic sites in hemoglobin and DNA. The products found in hemoglobin and the pattern of alkylation suggest that chloroacetaldehyde and S-(2-chloroethyl)glutathione are important reactive metabolites in vivo. The alkyl purines, 7-(2-oxoethyl)guanine and 7-[S-(2-cysteine)-ethyl]guanine, were found in DNA hydrolysates, as well as in the urine.
D000478:Alkylation; D000818:Animals; D001711:Biotransformation; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D005025:Ethylene Dichlorides / Q000378:metabolism* / Q000652:urine; D006454:Hemoglobins / Q000378:metabolism*; D006843:Hydrocarbons, Chlorinated / Q000378:metabolism*; D051379:Mice; D008808:Mice, Inbred CBA
D005025:Ethylene Dichlorides; D006454:Hemoglobins; D006843:Hydrocarbons, Chlorinated; C024565:ethylene dichloride; D004247:DNA