Trichloroethylene liver toxicity in mouse and rat: Microarray analysis reveals species differences in gene expression

Yuri Sano, Hiroshi Nakashima, Noriyuki Yoshioka, Norihito Etho, Tetsuo Nomiyama, Yuji Nishiwaki, Toru Takebayashi, Kazuyuki Oame

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

Trichloroethylene (TCE), an industrial organic solvent found in the environment, is a known carcinogen in laboratory animals and is believed to be carcinogenic in humans. Its carcinogenicity is subject to species-specific differences in biological activity, causing hepatocellular carcinoma in mouse and renal-cell carcinoma in rat. We have sought to better understand TCE's mode of action (MOA) by studying the alterations in gene expression profiles of liver in mice and rats that were administrated TCE by oral gavage either once or daily for 14 days. Microarray analysis revealed distinct transcriptional profiles and differences in biological pathways not only species-specific, but also pulse-dose effects within each species. For example, inhibition of the TGF-β pathway and activation of MAPK signaling were specific to mice repeatedly exposed to TCE. A better understanding of the MOA in mice and rats will lead to better hypotheses of TCE's affect on humans.

Original languageEnglish
Pages (from-to)835-849
Number of pages15
JournalArchives of Toxicology
Volume83
Issue number9
DOIs
Publication statusPublished - 2009 Sep 1

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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