KMID : 1038620220400010066
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Radiation Oncology Journal 2022 Volume.40 No. 1 p.66 ~ p.78
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PA1 cells containing a truncated DNA polymerase ¥â protein are more sensitive to gamma radiation
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Patra Anutosh
Nag Anish Chakraborty Anindita Bhattacharyya Nandan
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Abstract
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Purpose: DNA polymerase ¥â (Pol¥â) acts in the base excision repair (BER) pathway. Mutations in DNA polymerase ¥â (Pol¥â) are associated with different cancers. A variant of Pol¥â with a 97 amino acid deletion (Pol¥â¥Ä), in heterozygous conditions with wild-type Pol¥â, was identified in sporadic ovarian tumor samples. This study aims to evaluate the gamma radiation sensitivity of Pol¥â¥Ä for possible target therapy in ovarian cancer treatment.
Materials and Methods: Pol¥â¥Ä cDNA was cloned in a GFP vector and transfected in PA1 cells. Stable cells (PA1Pol¥â¥Ä) were treated with 60Co sourced gamma-ray (0?15 Gy) to investigate their radiation sensitivity. The affinity of Pol¥â¥Ä 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 PA1Pol¥â¥Ä cells in comparison with normal PA1 cells. Ten Gy of gamma radiation was found to be the optimal dose. Significantly more PA1Pol¥â¥Ä 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 Pol¥â¥Ä has more substantial binding potential towards the dsDNA than wild-type Pol¥â, suggesting a possible failure of BER pathway that results in cell death.
Conclusion: Our study showed that the PA1Pol¥â¥Ä 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.
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KEYWORD
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DNA polymerase ¥â, DNA repair, Ovarian epithelial carcinoma, Radiotherapy, Molecular docking simulation
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