The mutagenic effect of 1,2-dichloroethane on Salmonella typhimurium I. Activation through conjugation with glutathion in vitro.
One of the main components in the waste products from vinyl chloride industries (EDC-tar), is ethylene dichloride (1,2-dichloroethane). This compound has been tested for mutagenicity on Salmonella typhimurium TA 1535. It is concluded that 1,2-dichloroethane gives a weak direct mutagenic effect, which is enhanced by addition of the postmitochondrial liver fraction (S-9). This activation is NADPH-independent and non microsomal. It is caused by a factor in the soluble fraction (115 000 g supernatant). This activation was further enhanced by the addition of glutathione but not by the addition of L-cysteine, N-acetyl-L-cysteine or 2-mercaptoethanol. No activation was observed when glutathione was added in the presence of a totally denaturated S-9 fraction or in the absence of this fraction. Activation of 1,2-dichloroethane was also found in the presence of glutathione and glutathione S-transferase A and C but not with glutathione S-tranferase B. A synthetic conjugate S-(2-chloroethyl)-L-cysteine gave a strong direct mutagenic effect at concentrations where no effects were seen with 1,2-dichloroethane. It is thus concluded that 1,2-dichloroethane is activated by conjugation to glutathione. Another main component in EDC-tar, 1,1,2-trichloroethane, was not mutagenic under any of our experimental conditions. For comparison 1,2-dibromoethane was also tested and gave a stronger direct mutagenic effect than 1,2-dichloroethane. Like the latter 1,2-dibromoethane was also activated by a NADPH-independent process.
D000818:Animals; D003545:Cysteine / Q000378:metabolism; D005025:Ethylene Dichlorides / Q000378:metabolism / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism*; D006843:Hydrocarbons, Chlorinated / Q000494:pharmacology*; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D009153:Mutagens; D009249:NADP / Q000378:metabolism; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects*; D013347:Subcellular Fractions / Q000378:metabolism
D005025:Ethylene Dichlorides; D006843:Hydrocarbons, Chlorinated; D009153:Mutagens; D009249:NADP; D005978:Glutathione; D003545:Cysteine