Trichloroethylene liver toxicity in mouse and rat: microarray analysis reveals species differences in gene expression.
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-beta 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.
Sano
Yuri
Y
Department of Preventive Medicine and Public Health, Keio University School of Medicine, Tokyo, Japan. sanoyuri55@hotmail.com
Nakashima
Hiroshi
H
Yoshioka
Noriyuki
N
Etho
Norihito
N
Nomiyama
Tetsuo
T
Nishiwaki
Yuji
Y
Takebayashi
Toru
T
Oame
Kazuyuki
K
D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects*; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology; D008297:Male; D051379:Mice; D046228:Microarray Analysis / Q000379:methods*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012997:Solvents / Q000494:pharmacology*; D013045:Species Specificity; D014241:Trichloroethylene / Q000378:metabolism / Q000494:pharmacology*
D002273:Carcinogens; D012997:Solvents; D014241:Trichloroethylene