Gene expression analysis of toxicological pathways in TM3 leydig cell lines treated with Ethane dimethanesulfonate.
Ethane dimethanesulfonate (EDS), a well-known alkylating agent, selectively destroys Leydig cells. To clarify the molecular pathways underlying EDS action on Leydig cells, we analyzed gene expression profiles of an EDS-treated TM3 Leydig cell line. In this study, we analyzed the representative canonical pathways and toxicity pathways/gene lists using the Ingenuity Pathways Analysis program. In TM3 cells, 677 and 6756 genes were identified as being up- or downregulated after 3 and 24 h EDS treatments, respectively, (>1.3-fold changes, p < 0.05). Toxicological pathway analysis revealed that expression of genes related to Nrf2-mediated oxidative stress response showed remarkable changes in early or later stage of EDS-treated TM3 cells. Several genes related to steroidogenesis and apoptosis were also differentially expressed at 24 h in EDS-treated TM3 cells. Overall, toxicological pathway analysis using gene expression profiling showed that oxidative stress might be an important factor in cell death in TM3 cells affected by EDS treatment.
Division of Research and Development, Korea Institute of Toxicology, Daejeon, 305-343, Republic of Korea.
Eun-Hee
EH
Lee
Jung-Hwa
JH
Oh
Young-Sook
YS
Lee
Han-Jin
HJ
Park
Mi-Sun
MS
Choi
Se-Myo
SM
Park
Seung-Jun
SJ
Kang
Seokjoo
S
Yoon
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002460:Cell Line; D020869:Gene Expression Profiling; D007985:Leydig Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008698:Mesylates / Q000633:toxicity*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress; D013256:Steroids / Q000096:biosynthesis
D008698:Mesylates; D013256:Steroids; C002994:ethylene dimethanesulfonate