PA1 cells containing a truncated DNA polymerase β protein are more sensitive to gamma radiation

• 발행기관: 대한방사선종양학회
• 저자명: Anutosh Patra Anish Nag Anindita Chakraborty Nandan Bhattacharyya
• 간행물 정보: 『대한방사선종양학회지』제40권 제1호, 66~78쪽, 전체 13쪽
• 주제분류: 의약학 > 종양학
• 파일형태: PDF
• 발행일자: 2022.03.30

영문 초록

Purpose: DNA polymerase β (Polβ) acts in the base excision repair (BER) pathway. Mutations in DNA polymerase β (Polβ) are associated with different cancers. A variant of Polβ with a 97 amino acid deletion (PolβΔ), in heterozygous conditions with wild-type Polβ, was identified in sporadic ovarian tumor samples. This study aims to evaluate the gamma radiation sensitivity of PolβΔ for possible target therapy in ovarian cancer treatment. Materials and Methods: PolβΔ cDNA was cloned in a GFP vector and transfected in PA1 cells. Stable cells (PA1PolβΔ) were treated with 60Co sourced gamma-ray (0-15 Gy) to investigate their radiation sensitivity. The affinity of PolβΔ with DNA evaluated by DNA protein in silico docking experiments. Results: The result showed a statistically significant (p < 0.05) higher sensitivity towards radiation at different doses (0-15 Gy) and time-point (48-72 hours) for PA1PolβΔ cells in comparison with normal PA1 cells. Ten Gy of gamma radiation was found to be the optimal dose. Significantly more PA1PolβΔ cells were killed at this dose than PA1 cells after 48 hours of treatment via an apoptotic pathway. The in silico docking experiments revealed that PolβΔ has more substantial binding potential towards the dsDNA than wild-type Polβ, suggesting a possible failure of BER pathway that results in cell death. Conclusion: Our study showed that the PA1PolβΔ cells were more susceptible than PA1 cells to gamma radiation. In the future, the potentiality of ionizing radiation to treat this type of cancer will be checked in animal models.

목차

Introduction

Material and Methods

Results

Discussion and Conclusion

Conflict of Interest

Acknowledgements

Supplementary Materials

References

키워드

DNA polymerase β DNA repair Ovarian epithelial carcinoma Radiotherapy Molecular docking simulation