Genotoxicity of 1,1-dichloroethane.
1,1-Dichloroethane is covalently bound to macromolecules of rat and mouse organs in vivo after ip injection. Covalent Binding Index is typical of initiators classified as weak carcinogens. In vitro binding of 1,1-dichloroethane to nucleic acids and proteins is mediated by liver P-450-dependent microsomal mixed function oxidase system. Lung microsomes are weakly efficient whereas kidney and stomach microsomal fractions are uneffective. Interaction with macromolecules is enhanced by pretreatment with phenobarbitone and suppressed by 2-diethyl-aminoethyl-2,2-diphenyl valerate. Cytosolic enzymes from all of tested organs do not catalyze binding to macromolecules. GSH and/or cytosol addition to microsomal system determine a decrement or suppression of binding extent. This fact suggests that GSH plays a detoxificant role in 1,1-dichloroethane metabolism as for some other chlorinated compounds occurs.
Colacci
A
A
Arfellini
G
G
Mazzullo
M
M
Prodi
G
G
Grilli
S
S
D000818:Animals; D001711:Biotransformation; D004247:DNA / Q000378:metabolism; D005025:Ethylene Dichlorides / Q000378:metabolism / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008861:Microsomes / Q000378:metabolism; D009696:Nucleic Acids / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D005025:Ethylene Dichlorides; D006843:Hydrocarbons, Chlorinated; D009696:Nucleic Acids; D011506:Proteins; D012313:RNA; D004247:DNA; D005978:Glutathione