The influence of reduced glutathione on chromosome damage induced by X-rays or heavy ion beams of different LETs and on the interaction of DNA lesions induced by radiations and bleomycin

Pujari, Geetanjali; Sarma, Asitikantha; Chatterjee, Anupam

doi:10.1016/j.mrgentox.2010.01.006

Cited by 10 publications

(13 citation statements)

References 29 publications

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“…This data implicated that quality and quantity of DNA breaks were different for carbon ion and gamma. A large number of reports showed that high LET radiation such as carbon ion beam produced cluster DNA damage where huge number of DNA breaks was found in a very small region of DNA resulting higher number of DSBs [48–51]. The number of DNA breaks by low LET gamma in a particular region of DNA is far less than that of high LET radiation.…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2014

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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.

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Section: Resultsmentioning

confidence: 99%

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

et al. 2014

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“…Although a relationship linking oxidative stress and genomic instability has been reported [20], [21], data related to the modulation of antioxidant defenses (such as GSH) are still conflicting. For example, whatever the radiation quality, an increase in the endogenous GSH pool may inhibit sister chromatid exchange [22], increase exchange aberrations [19], or reduce the frequency of aberrant metaphases [18]. Deletion is the only common type of CC reported in previous studies that demonstrate that the number of deletions correlates inversely with GSH level [18], [19], [23], [24].…”

Section: Introductionmentioning

confidence: 98%

“…Nevertheless, only limited and conflicting data are available regarding the relationship between GSH level and high linear energy transfer (LET) and low-LET radiation-induced DNA damage. For example, Mansour et al [17] reported that N -acetylcysteine, a GSH precursor, protects hepatic tissues from radiation-induced DNA lesions, whereas other studies suggested a weak protector role of exogenous GSH on DNA lesions in lymphocytes or CHO cells [18], [19].…”

Section: Introductionmentioning

confidence: 99%

“…For example, whatever the radiation quality, an increase in the endogenous GSH pool may inhibit sister chromatid exchange [22], increase exchange aberrations [19], or reduce the frequency of aberrant metaphases [18]. Deletion is the only common type of CC reported in previous studies that demonstrate that the number of deletions correlates inversely with GSH level [18], [19], [23], [24]. Although an increasing number of data are available, with explanations or hypotheses linking these observations to the initial radioinduced DNA lesions, data on the repair capacity or the risk of CC transmission to the cell progeny are still lacking.…”

Section: Introductionmentioning

confidence: 99%

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Glutathione Depletion and Carbon Ion Radiation Potentiate Clustered DNA Lesions, Cell Death and Prevent Chromosomal Changes in Cancer Cells Progeny

et al. 2012

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Poor local control and tumor escape are of major concern in head-and-neck cancers treated by conventional radiotherapy or hadrontherapy. Reduced glutathione (GSH) is suspected of playing an important role in mechanisms leading to radioresistance, and its depletion should enable oxidative stress insult, thereby modifying the nature of DNA lesions and the subsequent chromosomal changes that potentially lead to tumor escape.This study aimed to highlight the impact of a GSH-depletion strategy (dimethylfumarate, and l-buthionine sulfoximine association) combined with carbon ion or X-ray irradiation on types of DNA lesions (sparse or clustered) and the subsequent transmission of chromosomal changes to the progeny in a radioresistant cell line (SQ20B) expressing a high endogenous GSH content. Results are compared with those of a radiosensitive cell line (SCC61) displaying a low endogenous GSH level.DNA damage measurements (γH2AX/comet assay) demonstrated that a transient GSH depletion in resistant SQ20B cells potentiated the effects of irradiation by initially increasing sparse DNA breaks and oxidative lesions after X-ray irradiation, while carbon ion irradiation enhanced the complexity of clustered oxidative damage. Moreover, residual DNA double-strand breaks were measured whatever the radiation qualities. The nature of the initial DNA lesions and amount of residual DNA damage were similar to those observed in sensitive SCC61 cells after both types of irradiation. Misrepaired or unrepaired lesions may lead to chromosomal changes, estimated in cell progeny by the cytome assay. Both types of irradiation induced aberrations in nondepleted resistant SQ20B and sensitive SCC61 cells. The GSH-depletion strategy prevented the transmission of aberrations (complex rearrangements and chromosome break or loss) in radioresistant SQ20B only when associated with carbon ion irradiation. A GSH-depleting strategy combined with hadrontherapy may thus have considerable advantage in the care of patients, by minimizing genomic instability and improving the local control.

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“…In general, high-LET radiation, such as alpha particles and heavy ions, generate clusters of damage along their trajectories in a medium, while low-LET radiation, such as X-rays and gamma rays, mainly induce dispersed damage, so high-LET radiation can induce more severe biological effects in cells [1]. It was also established that high- and low-LET radiation damage had different kinetics of induction and repair [2,3].…”

Section: Introductionmentioning

confidence: 99%

Effect of Photon Hormesis on Dose Responses to Alpha Particles in Zebrafish Embryos

Cheng

2017

IJMS

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Photon hormesis refers to the phenomenon where the biological effect of ionizing radiation with a high linear energy transfer (LET) value is diminished by photons with a low LET value. The present paper studied the effect of photon hormesis from X-rays on dose responses to alpha particles using embryos of the zebrafish (Danio rerio) as the in vivo vertebrate model. The toxicity of these ionizing radiations in the zebrafish embryos was assessed using the apoptotic counts at 20, 24, or 30 h post fertilization (hpf) revealed through acridine orange (AO) staining. For alpha-particle doses ≥ 4.4 mGy, the additional X-ray dose of 10 mGy significantly reduced the number of apoptotic cells at 24 hpf, which proved the presence of photon hormesis. Smaller alpha-particle doses might not have inflicted sufficient aggregate damages to trigger photon hormesis. The time gap T between the X-ray (10 mGy) and alpha-particle (4.4 mGy) exposures was also studied. Photon hormesis was present when T ≤ 30 min, but was absent when T = 60 min, at which time repair of damage induced by alpha particles would have completed to prevent their interactions with those induced by X-rays. Finally, the drop in the apoptotic counts at 24 hpf due to photon hormesis was explained by bringing the apoptotic events earlier to 20 hpf, which strongly supported the removal of aberrant cells through apoptosis as an underlying mechanism for photon hormesis.

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The influence of reduced glutathione on chromosome damage induced by X-rays or heavy ion beams of different LETs and on the interaction of DNA lesions induced by radiations and bleomycin

Cited by 10 publications

References 29 publications

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

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

Glutathione Depletion and Carbon Ion Radiation Potentiate Clustered DNA Lesions, Cell Death and Prevent Chromosomal Changes in Cancer Cells Progeny

Effect of Photon Hormesis on Dose Responses to Alpha Particles in Zebrafish Embryos

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