Species difference in gene expression effect of trichloroethylene (TCE) between mouse and rat (rat)

TCE is a non-genotoxic hepatocarcinogen in mouse, but not in rat or human. Extrapolation of data from laboratory animals to humans is difficult due to species-specific differences. To identify molecular pathways and biological changes responsible for species-specific differences in hepatocarcinogenesis, we analyzed gene expression profiles of livers from B6C3F1 mice and SD rats administered TCE by oral gavage once or repeatedly every 24 hrs for 14 days. Gene expression analysis revealed distinct clusters of transcriptional profiles in single- and repeated-dose mice and rats. Pathway analysis showed differences in biological pathways between single- and repeated-dose mice and rats. Activation of the MAPK signaling cascade and ubiquitin-proteasome inhibitory function, as well as inhibition of TGF-beta signaling, were specific to mice and suggest a role in hepatocyte proliferation. Although pathological analysis showed no evidence of apoptosis, gene expression analysis revealed changes in apoptosis-related genes. In addition to the previously reported suppression of apoptosis, results in repeated-dose mice showed that toxicity induced by TCE in turn induces apoptosis.

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