To investigate the degree of sister chromatid exchange(SCE) induced by saccharin and benzo(a)pyrene, cultured human lymphocytes were treated with different concentrations of saccharin and benzo(a)pyrene. The frequency of SCEs was increased with increasing concentrations of saccharin or benzo(a)pyrene. In order to analyze the effect of DNA hypomethylation which induces SCEs, we treated 5-azacytidine (5-aza-C), and hypomethylating agent and saccharin or benzo(a)pyrene in human lymphocytes. As a results, the frequency of SCEs in the lymphocytes treated with 5-aza-C and saccharin was greater than that treated with saccharin only. Similar result was observed in the lymphocytes treated with 5-aza-C and benzo(a)pyrene at the same time. Our results suggest that DNA hypomethylation is responsible for instability of the DNA structure which means that DNA methylation is important for chromosome stability.