DNA repair and chromosomal alterations

Natarajan, A.T.; Palitti, F.

doi:10.1016/j.mrgentox.2008.08.017

Cited by 91 publications

(65 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is well established that after radiation, a broad range of DNA damages are induced such as base damage, single strand breaks (SSBs), and double strand breaks (DSBs) if initial damage on DNA is not repaired properly. Among them, DSBs is regarded as the most deleterious one for its ability to arouse homologous recombination (HR) (58)(59)(60)(61). Then, HR can further generate base insertion, depletion, translocation along with high carcinogenicity (59)(60)(61).…”

Section: Radioprotection At the Molecular Levelmentioning

confidence: 99%

Research progress in the radioprotective effect of superoxide dismutase

et al. 2012

View full text Add to dashboard Cite

Irradiation from diverse sources is ubiquitous and closely associated with human activity. Radiation therapy (RT), an important component of the multiple radiation origins, contributes significantly to oncotherapy by killing tumor cells. On the other hand, RT can also cause some undesired normal tissue injuries that afflict numerous cancer patients. Although many promising radioprotective agents are emerging, few of them have entered the market successfully due to various limitations. At present, the most accepted hypothesis for the radiation-caused injury involves reactive oxygen species (ROS) generation. Superoxide dismutase (SOD), the unique enzyme responsible for the dismutation of superoxide radicals, is expected to occupy an indispensable position in the treatment of ROS-mediated tissue injuries originating from exposure to radiation. This review focuses on the mechanism of radioprotection by SOD at the tissue or organ level, cellular level, and molecular level, respectively, in order to provide references for further investigation of radiation injury and development of new radioprotectors.

show abstract

Section: Radioprotection At the Molecular Levelmentioning

confidence: 99%

Research progress in the radioprotective effect of superoxide dismutase

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Although repair mechanisms such as homologous recombination and non-homologous end joining are important responses to double-strand DNA and chromosomal damage (39)(40)(41)(42)(43), cell-cycle regulation is perhaps the most important determinant of radiation sensitivity in G2 phase cells (32) and therapeutic radiosensitivity could be improved through modulation of the cell cycle (44). This hypothesis is corroborated by the results shown in Fig.…”

Section: ------------------------------------------------------------mentioning

confidence: 55%

G2-checkpoint abrogation in irradiated lymphocytes: A new cytogenetic approach to assess individual radiosensitivity and predisposition to cancer

Terzoudi

Hatzi²,

Barszczewska³

et al. 2009

Int J Oncol

View full text Add to dashboard Cite

Abstract. Increased yield of chromatid breaks, following in vitro G2-phase lymphocyte irradiation, can be a marker of individual radiosensitivity and cancer predisposing genes whose role is to respond to DNA damage. Mutations or polymorphisms of genes encoding DNA repair pathways may underlie the increased chromosomal radiosensitivity. However, genes that facilitate DNA damage recognition, using signal transduction pathways to activate cell cycle arrest and preserve genomic integrity, are perhaps the most important determinant. Based on the latter hypothesis, an individual radiosensitivity parameter (IRP) is introduced, which expresses, at individual level, the G2-checkpoint potential to facilitate DNA damage recognition and repair of radiation-induced chromosomal damage during G2 to M-phase transition. Based on this parameter a new methodology for assessment of individual radiosensitivity is proposed, which involves G2-checkpoint abrogation by caffeine to obtain the IRP values. To evaluate the proposed methodology, blood samples from 52 healthy donors were taken for inter-individual radiosensitivity analysis using both the conventional G2 chromosomal radiosensitivity assay as well as the new approach using caffeineinduced G2-checkpoint abrogation. The two assays were compared in experiments using samples from 5 hypersensitive patients, 3 AT-homozygotes, 3 AT-heterozygotes, and the GM15786, GM03188A, GM09899, HCC1937 and MCF-7 cell lines. Using the G2 chromosomal radiosensitivity assay, donors are predicted as G2 radiosensitive or normal, while according to the new approach, individuals can be classified as highly radiosensitive, radiosensitive, normal, radioresistant and highly radioresistant. Overall, the new approach provides better individual radiosensitivity discrimination and intraexperimental reproducibility. Therefore, the proposed methodology using IRP values may provide a clinically applicable predictive assay for individual radiosensitivity and predisposition to cancer.

show abstract

“…Double-strand breaks (DSBs) caused by IR activate the G 1 /S checkpoint and induces G 1 /S checkpoint arrest (24). DSBs are repaired in the p53-dependent (25) and independent (26) manner during G 1 /S checkpoint arrest.…”

Section: Discussionmentioning

confidence: 99%

Optimization of calyculin A-induced premature chromosome condensation assay for chromosome aberration studies

Miura

Blakely

2011

Cytometry

View full text Add to dashboard Cite

Calyculin A-induced premature chromosome condensation (PCC) assay is a simple and useful method to assess structural and numerical chromosome aberrations in cells. Our hypothesis in this study is that suboptimum calyculin A induction of PCC resulting in fuzzy compactness and/or shortened length chromosomes would decrease the detection sensitivity of numerical and structural chromosome aberrations such as small PCC rings and small excess fragments. In this study, an optimization of calyculin A exposure on chromosome morphology and PCC induction frequency was investigated using a human peripheral blood lymphocyte (PBL) ex vivo irradiation ( 60 Coc rays; $0.6 Gy/min; 0-30 Gy) model. Treatment with calyculin A (50 nM) for 15 and 30 min resulted in 11.3 AE 2.7 and 9.9 AE 1.6-fold increases in the frequency of G 2 /M-PCC cells with extended length chromosomes compared with the 60-min treated group over a broad dose range (0 to 20 Gy), respectively. The G 2 /M-PCC scoring index per PCC in 15-and 30-min treated groups was increased by 1.9 AE 0.2 (P 5 0.001) and 1.8 AE 0.2 (P 5 0.001) compared with the 60-min treated group over 0-20 Gy, respectively. The G 2 /M-PCC efficiency of 30-min treated group was highest in the three conditions (i.e., 15-, 30-, and 60-min treatment) of calyculin A exposure. Calyculin A (50 nM) treatment for 30 min before the 48-h harvest of mitogen-stimulated human PBL is optimum for the formation of suitable chromosome morphology necessary to assess structural chromosome aberrations induced by exposure to radiation using the chemical induced-PCC assay. Published 2011 Wiley Periodicals, Inc.

show abstract

DNA repair and chromosomal alterations

Cited by 91 publications

References 29 publications

Research progress in the radioprotective effect of superoxide dismutase

Research progress in the radioprotective effect of superoxide dismutase

G2-checkpoint abrogation in irradiated lymphocytes: A new cytogenetic approach to assess individual radiosensitivity and predisposition to cancer

Optimization of calyculin A-induced premature chromosome condensation assay for chromosome aberration studies

Contact Info

Product

Resources

About