Microarray analysis of altered gene expression in the TM4 Sertoli-like cell line exposed to chromium(III) chloride.
Chromium(III) chloride is a common human exposure metal that is a preconceptional carcinogen in mice, although it enters cells poorly, and is non-toxic and non-carcinogenic in most biologic systems. An indirect effect on sperm is postulated, and this effect might be mediated through the testicular Sertoli cells that influence spermatogenesis. To test this possibility, we exposed mouse TM4 Sertoli-like cultured cells to 1mM CrCl(3) x 6H(2)O, a non-toxic dose, for 7 days and then extracted mRNA for microarray analysis. The chromium(III) chloride had modest effects on the expression of many genes, in the range of 1.5-2.3-fold. These effects provided an opportunity for development of statistical approaches for sifting microarray data in a situation where differences were small. Data were winnowed by screening for those ratios that fell outside the 99% confidence limits and/or represented a > or = 50% change in expression in the three comparison pairs. Fifty-two genes/clones were significant after the Bonferroni adjustment for multiple comparisons. The largest average increase was observed for the transcription factor Bach2, and this increase was confirmed by RT-PCR. The results show that Cr(III) has significant effects on gene expression in a Sertoli-like cell line.
Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, National Institutes of Health, Box B, Building 538, Fort Detrick, Frederick, MD 21702, USA. rcheng@ncicrf.gov
Robert Y S
RY
Cheng
W Gregory
WG
Alvord
Douglas
D
Powell
Kazimierz S
KS
Kasprzak
Lucy M
LM
Anderson
D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors; D002273:Carcinogens / Q000633:toxicity*; D002460:Cell Line; D002712:Chlorides / Q000633:toxicity*; D017608:Chromium Compounds / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012708:Sertoli Cells / Q000187:drug effects* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
C491123:BACH2 protein, human; C102109:Bach2 protein, mouse; D050976:Basic-Leucine Zipper Transcription Factors; D002273:Carcinogens; D002712:Chlorides; D017608:Chromium Compounds; D012333:RNA, Messenger; D014157:Transcription Factors; C017133:chromous chloride