We investigated differential gene expression as a possible molecular mechanism responsible for cell transformation induced by beryllium. Using the Atlas Mouse 1.2 Microarray (Clontech), we studied expression of genes involved in cancer, stress response and DNA synthesis, repair and recombination in BALB/c-3T3 cells transformed with beryllium sulfate. Genes whose expression was at least twofold different in the transformed cells compared with nontransformed cells were as follows: cancer-related genes (9): ets-related transcription factor gene activated by ras, colony-stimulating factor gene, A-myb, sky, cot, c-fos, c-jun, c-myc and R-ras proto-oncogenes; stress response genes (5): HSP84, HSP86, heme oxygenase 2 gene, etoposide-induced p53-responsive gene and oxidative stress-induced gene; and DNA synthesis, repair and recombination genes (11): genes for MCM4 DNA replication licensing factor, MCM5 DNA replication licensing factor, PMS2 DNA mismatch repair, DNA excision repair, MSH2 DNA mismatch repair, Rad23 UV excision repair, Lupus Ku autoantigen, DNA ligase 1, Rad51 and Rad52. We have also found that the beryllium-induced transcriptional activation of c-fos and c-jun is dependent on pathways of protein kinase C and MAP kinase and independent of reactive oxygen species. These results indicate that alterations in the expression of genes related to cancer, stress response and DNA damage repair may be responsible for the cell transformation induced by beryllium.