Abstract: OBJECTIVE: To elucidate the molecular mechanism of low concentration of N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) that interfered with the function of EGFR- mediated cellular signal transduction pathway，by inducing the epidermal growth factor receptor(EGFR)clustering，which was similar to that of epidermal growth factor treatment. METHODS： Eukaryotic expression vector of EGFR cytoplasmic domain gene was constructed and transfected into Lec-1 cells. Then the recombinant EGFR cytoplasmic domain protein was purified，and treated with MNNG for 1 h，at concentrations of 0.25，0.5，and 1.0 μmol/L. Enzyme linked immunoassay was used to measure the protein tyrosine kinase activity of recombinant EGFR cytoplasmic domain. Untreated recombinant cytoplasmic domain protein tyrosine kinase was used as control. RESULTS：Compared with normal control group，tyrosine kinase activity of EGFR was significantly inhibited by 0.5 μmol/L MNNG (P＜0.01). CONCLUSION：Low concentration of MNNG interfered with the signal transduction pathway of EGFR by supressing its tyrosine kinase activity.

Key words: epidermal growth factor receptor, N-methyl-N'-nitro-N-nitrosoguanidine, tyrosine kinase