The frequency of micronucleus (MN) in the peripheral blood of mice exposed to monofunctional alkylating agents, such as ENU or MNU, in the dark period was higher than that in the light period (Itoh et al., J Toxicol Sci., 37, 1071-1076, 2012). We reported that difference of MN induction is caused by circadian rhythm of erythropoietin (EPO), which has anti-apoptotic effect (Itoh et al., J Toxicol Sci., 44, 273-282, 2019). And the relationship of mismatch repair (MMR) to the difference of MN induction was suggested because the no difference was observed in MN inductions between the light- and dark-period treatment of MNU in Msh2-/- mice (The 50th JEMS, Abstract, p126). To investigate the combined effects of MNU and EPO, in vitro MN tests were performed using TK6 cells which the genes of MMR related protein, MLH1 or MSH2, were knocked out. As the results, in MLH1 knock-out and MSH2 knock-out cells (These cells are gift from Prof. Takeda, Kyoto Univ.), no differences of MN induction were observed between the MNU treatments and control. And there were no increased MN induction by EPO treatments. In control TK6 cells, increased the frequency of MN inductions by MNU treatments were observed. Moreover, higher MN inductions were observed in the cells treated with MNU and EPO than in those with only MNU. These results suggested that EPO is involved in MMR and suppresses apoptosis, which results in increase of the frequency of MN induction by MNU in TK6 cells.