AIM and METHODES: To evaluate the possible signal transduction mechanism of nontargeted mutagenesis in vero cells induced by DNA damaging agent N-methyl-N-nitro-N-nitrosoguanidine(MNNG),the activation of c-Jun NH 2-terminal kinase/stress activated protein kinase(SAPK/JNK) pathway in vero cells induced by MNNG was studied. Western Blot analysis and Solid-phase kinase assay were used to measure the phosphorylation of JNK1 and kinase activity of JNKs, respectively. RESULTS: After 0.2 ?mol/L, 2.5 h MNNG or 1 mg/L, 1 h cycloheximide (CHM) treatment, the proportion of phosphorylated JNK1 in cell extract increased significantly, simultaneously the kinase activity of JNKs increased dramatically(6.7 and 3.0 folds respectively), as measured by the phosphorylation of c-Jun, a substrate of JNKs. CONCLUSION: Both 0.2 ?mol/L 2.5 h MNNG and 1 mg/L 1 h CHM treatment can induce the activation of JNK/SAPK pathway, one of the stress signal transduction pathways, in vero cells.