The mutagenic effect of 1,2-dichloroethane on Salmonella typhimurium I. Activation through conjugation with glutathion in vitro

Chem Biol Interact. 1978 Jan;20(1):1-16. doi: 10.1016/0009-2797(78)90076-5.

Abstract

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.

MeSH terms

  • Animals
  • Cysteine / metabolism
  • Ethylene Dichlorides / metabolism
  • Ethylene Dichlorides / pharmacology*
  • Glutathione / metabolism*
  • Hydrocarbons, Chlorinated / pharmacology*
  • In Vitro Techniques
  • Liver / metabolism
  • Liver / ultrastructure
  • Male
  • Mutagens*
  • NADP / metabolism
  • Rats
  • Salmonella typhimurium / drug effects*
  • Subcellular Fractions / metabolism

Substances

  • Ethylene Dichlorides
  • Hydrocarbons, Chlorinated
  • Mutagens
  • NADP
  • Glutathione
  • Cysteine