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.