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.
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Acknowledgments
This work was supported by the Ministry of Education, Science, and Culture of Japan (Grant-in-Aid for Science Research No.12307010 to K. O. and No. 16590483 to H. N.) and the Ministry of Health, Labor and Welfare of Japan (Health Labor Sciences Research Grant H12-seikatsu-002 to K.O.). We thank Dr. MS. Ko and Dr. GJ. Kargul for critical reading of the manuscript.
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Sano, Y., Nakashima, H., Yoshioka, N. et al. Trichloroethylene liver toxicity in mouse and rat: microarray analysis reveals species differences in gene expression. Arch Toxicol 83, 835–849 (2009). https://doi.org/10.1007/s00204-009-0431-1
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DOI: https://doi.org/10.1007/s00204-009-0431-1