OBJECTIVE@#To determine the effect and molecular mechanism of
DNA damage caused by
suicide gene therapy system HSV-TK/GCV under Tet-On
regulation in
human breast cancer cell line MCF-7 infected by recombinant
adeno-associated virus (rAAV).@*
METHODS@#We used
comet assay to detect the effect of HSV-TK/GCV
suicide gene regulation system on MCF-7
DNA damage, and analyzed the expression change of relative
DNA damage response active
genes and
proteins with RT-PCR and
Western blot.@*RESULTS@#Compared with other
control groups, the
comet assay showed that
MCF-7 cells with HSV-TK/GCV
treatment had obvious comet
tails, and the expression level of
DNA damage response active
genes and
proteins changed obviously in the HSV-TK/GCV
treatment group,such as ATM, p53 and p27,but CyclinE and CDK2 did not change.@*CONCLUSION@#
DNA damage on
MCF-7 cells is resulted from HSV-TK/GCV in
suicide gene therapy system through a p53-dependent
signal pathway, causing
cell cycle arrest and
cell death.