The mutagenic effect of 1,2-dichloroethane on Salmonella typhimurium. II. Activation by the isolated perfused rat liver.
In this investigation Salmonella typhimurium strain TA 1530 and TA 1535 were combined with isolated perfused rat liver. Samples of perfusate and bile produced were tested for mutagenicity after treatment with 1,2-dichloroethane (DCE), 1,2-dibromoethane (DBE) or 2-chloroethanol. The results are in good agreement with our previous experiments which indicate that both DEC and DBE are activated through conjugation with glutathione (GSH). Most GSH conjugates are normally excreted in bile. Following liver perfusion the bile was highly mutagenic after DCE and DBE treatments, while 2-chloroethanol did not have this effect. The highest mutagenic effect was seen 15--30 min after the addition of DCE or DBE. The production of mutagenic bile also occurred in mice treated in vivo with DCE. One possible metabolic endproduct of a GSH conjugate is the corresponding mercapturic acid. Thus synthetic N-acetyl-S-(2-chloroethyl)-L-cysteine was tested on TA 1535 and found to be as mutagenic as S-(2-chloroethyl)-L-cysteine in the concentration range 0.2--0.6 mumol/plate. Differences and similarities in the metabolism of DCE and vinyl chloride are discussed on the basis of these results.
D000818:Animals; D001711:Biotransformation; D003545:Cysteine / Q000031:analogs & derivatives / Q000633:toxicity; D005025:Ethylene Dichlorides / Q000378:metabolism / Q000633:toxicity*; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity*; D008658:Inactivation, Metabolic; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D009153:Mutagens; D010477:Perfusion; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics
D005025:Ethylene Dichlorides; D006843:Hydrocarbons, Chlorinated; D009153:Mutagens; D003545:Cysteine