Radiosensitivity and Induction of Apoptosis by High LET Carbon Ion Beam and Low LET Gamma Radiation: A Comparative Study

Cancer treatment with high LET heavy ion beam, especially, carbon ion beam (12C), is becoming very popular over conventional radiotherapy like low LET gamma or X-ray. Combination of Poly(ADP-ribose) polymerase (PARP) inhibitor with xenotoxic drugs or conventional radiation (gamma or X-ray) is the ne...

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Main Authors: Atanu Ghorai, Nitai P. Bhattacharyya, Asitikantha Sarma, Utpal Ghosh
Format: Article
Language:English
Published: Hindawi Limited 2014-01-01
Series:Scientifica
Online Access:http://dx.doi.org/10.1155/2014/438030
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spelling doaj-2bc05eeff9bc419291f086bc6146930d2020-11-25T02:01:16ZengHindawi LimitedScientifica2090-908X2014-01-01201410.1155/2014/438030438030Radiosensitivity and Induction of Apoptosis by High LET Carbon Ion Beam and Low LET Gamma Radiation: A Comparative StudyAtanu Ghorai0Nitai P. Bhattacharyya1Asitikantha Sarma2Utpal Ghosh3Department of Biochemistry & Biophysics, University of Kalyani, Kalyani 741235, IndiaCrystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700 064, IndiaInter-University Accelerator Center (IUAC), Aruna Asaf Ali Marg, New Delhi 110067, IndiaDepartment of Biochemistry & Biophysics, University of Kalyani, Kalyani 741235, IndiaCancer treatment with high LET heavy ion beam, especially, carbon ion beam (12C), is becoming very popular over conventional radiotherapy like low LET gamma or X-ray. Combination of Poly(ADP-ribose) polymerase (PARP) inhibitor with xenotoxic drugs or conventional radiation (gamma or X-ray) is the newer approach for cancer therapy. The aim of our study was to compare the radiosensitivity and induction of apoptosis by high LET 12C and low LET gamma radiation in HeLa and PARP-1 knocked down cells. We did comet assay to detect DNA breaks, clonogenic survival assay, and cell cycle analysis to measure recovery after DNA damage. We measured apoptotic parameters like nuclear fragmentation and caspase-3 activation. DNA damage, cell killing, and induction of apoptosis were significantly higher for 12C than gamma radiation in HeLa. Cell killing and apoptosis were further elevated upon knocking down of PARP-1. Both 12C and gamma induced G2/M arrest although the 12C had greater effect. Unlike the gamma, 12C irradiation affects DNA replication as detected by S-phase delay in cell cycle analysis. So, we conclude that high LET 12C has greater potential over low LET gamma radiation in killing cells and radiosensitization upon PARP-1 inhibition was several folds greater for 12C than gamma.http://dx.doi.org/10.1155/2014/438030
collection DOAJ
language English
format Article
sources DOAJ
author Atanu Ghorai
Nitai P. Bhattacharyya
Asitikantha Sarma
Utpal Ghosh
spellingShingle Atanu Ghorai
Nitai P. Bhattacharyya
Asitikantha Sarma
Utpal Ghosh
Radiosensitivity and Induction of Apoptosis by High LET Carbon Ion Beam and Low LET Gamma Radiation: A Comparative Study
Scientifica
author_facet Atanu Ghorai
Nitai P. Bhattacharyya
Asitikantha Sarma
Utpal Ghosh
author_sort Atanu Ghorai
title Radiosensitivity and Induction of Apoptosis by High LET Carbon Ion Beam and Low LET Gamma Radiation: A Comparative Study
title_short Radiosensitivity and Induction of Apoptosis by High LET Carbon Ion Beam and Low LET Gamma Radiation: A Comparative Study
title_full Radiosensitivity and Induction of Apoptosis by High LET Carbon Ion Beam and Low LET Gamma Radiation: A Comparative Study
title_fullStr Radiosensitivity and Induction of Apoptosis by High LET Carbon Ion Beam and Low LET Gamma Radiation: A Comparative Study
title_full_unstemmed Radiosensitivity and Induction of Apoptosis by High LET Carbon Ion Beam and Low LET Gamma Radiation: A Comparative Study
title_sort radiosensitivity and induction of apoptosis by high let carbon ion beam and low let gamma radiation: a comparative study
publisher Hindawi Limited
series Scientifica
issn 2090-908X
publishDate 2014-01-01
description Cancer treatment with high LET heavy ion beam, especially, carbon ion beam (12C), is becoming very popular over conventional radiotherapy like low LET gamma or X-ray. Combination of Poly(ADP-ribose) polymerase (PARP) inhibitor with xenotoxic drugs or conventional radiation (gamma or X-ray) is the newer approach for cancer therapy. The aim of our study was to compare the radiosensitivity and induction of apoptosis by high LET 12C and low LET gamma radiation in HeLa and PARP-1 knocked down cells. We did comet assay to detect DNA breaks, clonogenic survival assay, and cell cycle analysis to measure recovery after DNA damage. We measured apoptotic parameters like nuclear fragmentation and caspase-3 activation. DNA damage, cell killing, and induction of apoptosis were significantly higher for 12C than gamma radiation in HeLa. Cell killing and apoptosis were further elevated upon knocking down of PARP-1. Both 12C and gamma induced G2/M arrest although the 12C had greater effect. Unlike the gamma, 12C irradiation affects DNA replication as detected by S-phase delay in cell cycle analysis. So, we conclude that high LET 12C has greater potential over low LET gamma radiation in killing cells and radiosensitization upon PARP-1 inhibition was several folds greater for 12C than gamma.
url http://dx.doi.org/10.1155/2014/438030
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