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Detection of DCA production in vivo after TCE administration has been complicated by reported problems with analytical methodologies that have led to artifactual formation of DCA ex vivo when samples contain significant amounts of TCA (Ketcha et al. 1996).
The formation of DCA was hindered by the presence of excess water.
The investigation into the formation of DCA from the metabolism of DCP proved to be unsuccessful due to its rapid disappearance.
Indirect evidence for the formation of DCA could be provided by the analysis of further metabolites such as glutathione conjugates and protein adducts.
As discussed in the pharmacokinetics article in this mini-monograph (Chiu et al. 2006b), direct evidence for the formation of DCA from TCE is limited because of the difficulty in directly detecting DCA after TCE exposure.
On the basis of these observations, two main metabolic pathways were proposed, as shown in Figure 1, one via the formation of ECH and one via the formation of DCA.
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Formation of Mito-DCA was confirmed by spectroscopic and analytical methods.
Addition of a pool of all the antibodies completely abrogated the formation of the DCA-induced AP-1 complex.
To date, there is no direct evidence for the formation of ECH or DCA following exposure to DCP in rodents or humans.
Lash et al. (2000a) discussed two potential sources of DCA formation, from TCOH and from dechlorination of TCA.
As shown in Figure 5a, the addition of DCA induced the formation of PKM2 Oct4 complexes.
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