92145-83-0Relevant articles and documents
Immunochemical detection of protein adducts in mice treated with trichloroethylene
Halmes, N. Christine,McMillan, David C.,Oatis Jr., John E.,Pumford, Neil R.
, p. 451 - 456 (1996)
Trichloroethylene has been shown to produce tumors in rodents and is a suspect human carcinogen. In addition, a number of case reports raise the possibility that trichloroethylene can induce an autoimmune disorder known as systemic sclerosis. To investigate whether covalent binding of reactive trichloroethylene metabolites may be involved in the mechanisms underlying these toxic responses, we have developed a polyclonal antibody that can recognize trichloroethylene-protein adducts in tissues. The antibody was prepared by immunizing a rabbit with dichloroacetic anhydride-modified keyhole limpet hemocyanin. Enzyme-linked immunosorbent assay data indicated that the serum antibody recognized dichloroacetic anhydride-modified rabbit serum albumin, but not unmodified protein. In addition, N(ε)-dichloroacetyl- L-lysine was the most potent inhibitor of antibody binding to dichloroacetic anhydride-modified rabbit serum albumin, indicating that the antibody recognizes primarily dichloroacetylated lysine residues. Immunoblots revealed the presence of two major trichloroethylene adducts at 50 and 100 kDa in liver microsomal fractions from male B6C3/F1 mice treated with trichloroethylene. The formation of trichloroethylene adducts was both dose and time dependent. Furthermore, the 50-kDa adduct was found to comigrate on a polyacrylamide gel with cytochrome P450 2E1. These data show that reactive metabolites of trichloroethylene are formed in vivo and bind covalently to discrete proteins in mouse liver. The data also suggest that one of the protein targets is cytochrome P450 2E1. Further studies will be necessary to elucidate the relationship between covalent binding of trichloroethylene and trichloroethylene toxicity.
Mechanism of aqueous decomposition of trichloroethylene oxide
Cai, Hongliang,Guengerich, F. Peter
, p. 11656 - 11663 (2007/10/03)
The aqueous decomposition of trichloroethylene (TCE) oxide is shown to involve both pH-independent and hydronium ion-dependent regions. C-C bond scission is a major reaction at all pH values. Disappearance of TCE oxide is the rate-determining step for the formation of CO under the conditions studied. The product distribution of CO and three carboxylic acids (HCO2H, Cl2CHCO2H, and glyoxylic acid) did not change considerably over the pH range of -1.5-14, in general, even though the hydrolysis mechanism changes from hydronium ion-dependent to pH-independent. Mechanisms for the hydronium ion-dependent and pH-independent hydrolysis of TCE oxide were elucidated on the basis of the results of H218O and H incorporation and identification of products of the reaction of TCE oxide with lysine in both H216O and H218O. In the pH-independent hydrolysis, a zwitterionic intermediate could be formed and undergo an intramolecular rearrangement (Cl- shift) to generate dichloroacetyl chloride, which would subsequently decompose to Cl2CHCO2H. The zwitterionic intermediate could also hydrolyze at the less sterically hindered methylene to give a glycol anion, which would dehydrohalogenate to form an oxoacetyl chloride intermediate. The oxoacetyl chloride could hydrolyze to generate either glyoxylic acid, as a final product, or an anionic intermediate, which could go through a concerted mechanism to generate CO, HCO2H, and chloride. A mechanism proposed for the hydronium ion-dependent hydrolysis is very similar to that for the pH-independent hydrolysis except for the first step, which involves hydronium ion attack on TCE oxide to form a TCE-oxide cation intermediate. The lysine amide adducts were characterized by HPLC and mass spectrometry as those resulting from reaction with the postulated acyl chlorides.
