Correlation of micronuclei-induction with the cell survival in HeLa cells treated with a base analogue, azidothymidine (AZT) before exposure to different doses of γ-radiation

Jagetia, Ganesh Chandra; Aruna, R

doi:10.1016/s0378-4274(02)00439-3

Cited by 15 publications

(12 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One outcome of IR-induced DNA damage is the generation of acentric chromosomes that develop into circular chromatinbound micronuclei after cells complete one or more cycles of mitotic division (32)(33)(34). Three mutant EGFR NSCLCs, H820, H1975, and H2279, showed an IR dose-dependent increase in micronuclei, which were absent in WT EGFR-expressing cell lines Figure 3.…”

Section: Cancer Researchmentioning

confidence: 99%

Non–Small Cell Lung Cancers with Kinase Domain Mutations in the Epidermal Growth Factor Receptor Are Sensitive to Ionizing Radiation

Das¹,

Sato

Story³

et al. 2006

Cancer Research

198

172

View full text Add to dashboard Cite

Non-small cell lung cancers (NSCLCs) bearing mutations in the tyrosine kinase domain (TKD) of the epidermal growth factor receptor (EGFR) often exhibit dramatic sensitivity to the EGFR tyrosine kinase inhibitors gefitinib and erlotinib. Ionizing radiation (IR) is frequently used in the treatment of NSCLC, but little is known how lung tumor-acquired EGFR mutations affect responses to IR. Because this is of great clinical importance, we investigated and found that clonogenic survival of mutant EGFR NSCLCs in response to IR was reduced 500-to 1,000-fold compared with wild-type (WT) EGFR NSCLCs. Exogenous expression of either the L858R point mutant or the #E746-E750 deletion mutant form of EGFR in immortalized human bronchial epithelial cells, p53 WT NSCLC (A549), or p53-null NSCLC (NCI-H1299) resulted in dramatically increased sensitivity to IR. We show that the majority of mutant EGFR NSCLCs, including those that contain the secondary gefitinib resistance T790M mutation, exhibit characteristics consistent with a radiosensitive phenotype, which include delayed DNA repair kinetics, defective IR-induced arrest in DNA synthesis or mitosis, and pronounced increases in apoptosis or micronuclei. Thus, understanding how activating mutations in the TKD domain of EGFR contribute to radiosensitivity should provide new insight into effective treatment of NSCLC with radiotherapy and perhaps avoid emergence of single agent drug resistance.

show abstract

Section: Cancer Researchmentioning

confidence: 99%

Non–Small Cell Lung Cancers with Kinase Domain Mutations in the Epidermal Growth Factor Receptor Are Sensitive to Ionizing Radiation

Das¹,

Sato

Story³

et al. 2006

Cancer Research

198

172

View full text Add to dashboard Cite

show abstract

“…No changes were noted in average radiation-induced MN yields of the HCWs at the different time points. Jagetia and Aruna [25], found that administration of AZT to Hela cells before exposure to different doses of γ-radiation resulted in a significant elevation in the yield of MN. This was in contrast to Copaceanu et al [26] who suggested radioprotection of AZT in Hela cell lines exposed to irradiation in-vitro.…”

Section: Discussionmentioning

confidence: 99%

“…Since NRTIs interact with host DNA, inhibit mammalian DNA polymerases and affect the cell cycle [21], it is possible that they have an impact on DNA damage repair and affect chromosomal radiosensitivity. Some studies have shown antiretroviral drugs to be radioprotective while others have suggested a radiosensitising effect [25,26]. For the first part of this study we investigated the chromosomal radiosensitivity of HIV patients not on ART, HIV patients on two common ART regimens (d4T+3TC+EFV and TDF+3TC+EFV) and compared it to healthy uninfected controls.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The Effect of HIV and Antiretroviral Therapy on Chromosomal Radiosensitivity

Herd¹,

Francies²,

Slabbert³

et al. 2014

J AIDS Clin Res

View full text Add to dashboard Cite

Introduction: Antiretroviral Treatment (ART) has led to an improvement in survival of HIV infected individuals. Some of them will develop cancer during the course of their infection and will require radiation therapy. HIV positive cancer patients have presented with adverse side effects of radiotherapy and elevated chromosomal radiosensitivity. This study investigated if ART has an influence on chromosomal radiosensitivity of HIV positive individuals. Methods and Materials:Blood samples from 60 HIV positive individuals were in vitro exposed to doses of X-rays of 0, 2 and 4Gy and chromosomal radiosensitivity was assessed with the micronucleus assay. The micronucleus assay was also performed on lymphocytes of a group of non HIV-infected health care workers taking prophylactic post-exposure ART to measure the effect of these ART drugs on chromosomal radiosensitivity without HIV as a confounding factor.Results: All HIV patients (those on ART and without ART) had significantly higher radiation induced Micronuclei (MN) than healthy controls. The MN yields increased in the HIV patients taking ART compared to HIV patients not on treatment. The evaluation of chromosomal radiosensitivity of health care workers on ART revealed no effects of ART. Conclusions:HIV positive individuals show an increased chromosomal radiosensitivity. Antiretroviral treatment given to HIV positive individuals can lead to enhanced chromosomal radiosensitivity and therefore impose higher risks for radiotherapy side effects in these patients.

show abstract

“…For example, AZT is known to disturb nucleotide metabolism, (34) and separating the effects of this disturbance from the effects of RT inhibition is difficult. Thus reports that AZT inhibits proliferation (35) and DNA repair, (35) and is mutagenic (36) or radio-sensitising (37) do not on their own provide evidence for TT-HDR. More detailed analyses of the effects of RT inhibitors may be informative, however.…”

Section: Sensitivity To Rt Inhibitionmentioning

confidence: 97%

Hypothesis: transcript‐templated repair of DNA double‐strand breaks

Trott

Porter

2005

BioEssays

View full text Add to dashboard Cite

Two mechanisms are available for the repair of DNA double-strand breaks (DSBs) in eukaryotic cells: homology directed repair (HDR) and non-homologous end-joining (NHEJ). While NHEJ is not restricted to a particular phase of the cell cycle, it is incapable of accurately repairing DBSs that have suffered a loss or gain of nucleotide sequence information. In contrast, HDR achieves accurate repair of such DSBs by use of a sister chromatid as a DNA template, but is restricted to cell cycle phases (S/G2) when such templates are available. In this scheme, G1 cells appear to lack a mechanism for the accurate repair of certain DSBs, and an ability to use alternative templates would be highly advantageous. Considered here, therefore, is the possibility that RNA transcripts are used as templates for HDR. Potential mechanisms for transcript-templated HDR, and ways in which it might be detected, are presented.

show abstract

Correlation of micronuclei-induction with the cell survival in HeLa cells treated with a base analogue, azidothymidine (AZT) before exposure to different doses of γ-radiation

Cited by 15 publications

References 25 publications

Non–Small Cell Lung Cancers with Kinase Domain Mutations in the Epidermal Growth Factor Receptor Are Sensitive to Ionizing Radiation

Non–Small Cell Lung Cancers with Kinase Domain Mutations in the Epidermal Growth Factor Receptor Are Sensitive to Ionizing Radiation

The Effect of HIV and Antiretroviral Therapy on Chromosomal Radiosensitivity

Hypothesis: transcript‐templated repair of DNA double‐strand breaks

Contact Info

Product

Resources

About