hMSH2 deficiency of DNA repair enzyme and cell genetic stability

  Objective   To study the relationship between hMSH2-deficiency and cell genetic instability.

  Methods   After being administered by methyl methanesulphonate (MMS), 50% inhibitory concentration (IC₅₀) of cell viability, rates of abnormal nuclei and that of micronuclei (MN) were detected in HLF and HLFS.

  Results   The IC₅₀ and HLF to MMS in 24 hours was 7.9 0 μmol/L, while that of HLFS was 89.13 μmol/L.Six dose groups of both HLF and HLFS were assessed, in which there were positive dose-effect relationships between the rates of micronuclei and doses (P < 0.05).The rates of micronuclei were different significantly (P < 0.05 or P < 0.01) between middle and high dose groups v.s control group in either HLF or HLFS. The rates of micronuclei were different significantly between HLF and HLFS in 4μmol/L and 8μmol/L group, while that in 1 μmol/L and 2 μmol/L group showed no difference. The rates of micronuclei in HLFS seem higher than that in HLF, but no statistically significant difference was observed, while no interaction between administration and transfection (P > 0.05) was found. In all of the dose groups, the rates of abnormal nuclei in HLFS were higher significantly than that in HLF (P=0.000). There was no significant difference in rates of abnormal nuclei between administering group and control group. Intotal, the rates of abnormal nuclei in HLFS were higher than that in HLF significantly (P < 0.01).In term of forming abnormal nuclei, there were no interation between administration and transfection and no dose-effect relationship between rates of abnormal nuclei and doses.

  Conclusion   The hMSH2 deficiency of DNA repair enzyme resulted in alkylation tolerance, rates of abnormal nuclei and micronuclei increasing, which suggested that hMSH2 deficiency may increase the cellular genetic instability.