Mechanisms Involved in Trichloroethylene-Induced Liver Cancer: Importance to Environmental Cleanup
The project is organized around two interrelated tasks: Task 1 develops the basic dosimetry parameters and provides in vivo data describing the mode of action tumorigenic and for the metabolites of TCE that produce liver cancer in mice, dichloroacetate (DCA) and trichloroacetate (TCA). Early work suggested that TCA was primarily responsible for TCE-induced liver tumor. More recent, mechanistic observations indicated that DCA played a prominent role. Therefore, studies were designed to determine whether the effects of DCA were mediated through a mode of action that affects primarily tumor growth rates. Task 2 seeks specific evidence that TCA and DCA are capable of promoting the growth of spontaneously initiated cells from mouse liver, in vitro. The data provide the clearest evidence that both metabolites act by a mechanism of selection rather than mutation. These data are necessary to select between a linear (i.e. no threshold) and non-linear low-dose extrapolation models.
- Research Organization:
- Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
- Sponsoring Organization:
- USDOE Office of Environmental Management (EM) (US)
- OSTI ID:
- 827059
- Report Number(s):
- EMSP-54684-2000; R&D Project: EMSP 54684; TRN: US200425%%225
- Resource Relation:
- Other Information: PBD: 1 Jun 2000
- Country of Publication:
- United States
- Language:
- English
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