Abstract
Purpose: 5-azacitidine (5-Aza-CR), a DNA methyltransferase inhibitor used in some clinical trials, shows anti-tumor activity by inhibiting methylation of several tumor suppressor genes. On the other hand, 5-Aza-CR shows cytotoxicity. Some report say 5-Aza-CR activates apoptotic pathway via p53. We estimated the effect of 5-Aza-CR on radiosensitivity of cell lines with wild or mutant p53.
Materials and methods: human non-small lung cancer cell lines with p53 null type transfected with neomycine resistant vector (H1299/neo) or with wild type p53 (H1299/wp53) or mutant p53 (H1299/mp53) were used in the experiment. Cells were subcultured in D-MEM containing 10% of fetal bovine serum at 37C in 5% CO2 atmosphere. Cells with exponentially growing phase were used in the experiment. Radiation was given by 10MV linac X-ray. Cell viability was estimated by colony forming ability.
Results: Plating efficiency of 3 cell lines declined around 30% of control by exposing the cells to 100uM of 5-Aza-CR for 48 hours. No difference in cytotoxicity of 5-Aza-CR was seen between 3 cell lines. 5-Aza-CR slightly enhanced radiosensitivity of H1299/wp53 cell line, while in H1299/neo and H1299/mp53 cell lines, 5-Aza-CR showed no modification effect in radiosensitivity.
Conclusion: 5-Aza-CR slightly enhanced radiosensitivity of cell lines with wild type p53.
