Radiobiological Response of Cervical Cancer Cell Line in Low Dose Region: Evidence of Low Dose Hypersensitivity (HRS) and Induced Radioresistance (IRR)

Das, Saikat; Singh, Rabiraja; George, Daicy; Vijaykumar, T.S.; John, Subhashini

doi:10.7860/jcdr/2015/14120.6074

Cited by 5 publications

(6 citation statements)

References 16 publications

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“…We observed that the combined treated cells at 0·5 Gy gives the highest expression. Previous studies have shown that HeLa cells are known to exhibit hyper-radiosensitivity at radiation dose <1 Gy 9 . This correlates with our study in Figure 4.…”

Section: Resultssupporting

confidence: 93%

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Quantification of DNA double-strand break induced by radiation in cervix cancer cells: in vitro study

et al. 2018

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AimDNA double-strand break (DSB) results in the phosphorylation of the protein, H.2AX histone. In this study, the effect of radiotherapy and chemotherapy on DNA DSB in cervical cancer cells is analysed by the phosphorylation of the protein.MethodsThe cervical cancer cells (HeLa cells) were cultured and exposed to ionising radiation. Radiation sensitivity was measured by clonogenic survival fraction after exposing to ionising radiation. Since the phosphorylation of H.2AX declines with time, the DNA damage was quantified at different time points: 1 hour, 3 hours and 1 week after exposed to the radiation. The analysis of γ-H.2AX was done by Western-blot technique. The protein expression was observed at different dose of radiation and combination of both radiation and paclitaxel.ResultsLow-dose hypersensitivity was observed. By 1 week after radiation at 0·5, 0·8 and 2 Gy, there was no expression of phosphorylated H.2AX. Previous experiments on the expression of phosphorylated H.2AX (γ-H.2AX) in terms of foci analysis was found to peak at 1 hour and subsequently decline with time. In cells treated with the DNA damaging agents, the expression of phosphorylated H.2AX decreases in a dose-dependent manner when treated with radiation alone. However, when combined with paclitaxel, at 0·5 Gy, the expression peaked and reduces at 0·8 Gy and slightly elevated at 2 Gy.FindingsIn this study, the peak phosphorylation was observed at 3 hour post irradiation indicating that DSBs are still left unrepaired.

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Section: Resultssupporting

confidence: 93%

“…Previous studies have shown that HeLa cells are known to exhibit hyper-radiosensitivity at radiation dose <1 Gy. 9 This correlates with our study in Figure 4. In addition, the cell survival curve for cells irradiated with radiation in conjunction with chemotherapeutic drug is steeper than the curve for cells with radiation alone.…”

Section: Resultssupporting

confidence: 92%

Quantification of DNA double-strand break induced by radiation in cervix cancer cells: in vitro study

et al. 2018

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“…The terminal portion of the survival curve follows an exponential relationship indicating that the radiation dose increment is proportional to the reduction of the survival fraction. However, doses between 0 and 0.5 Gy follows a typical pattern indicative of a transition between the low dose hypersensitive region and an induction of radio-resistance (Das et al 2015). This is seen to closely follow the induced repair model (R 2 = 0.97, p < 0.05) with the increased cell counts at doses lower than 0.25 Gy.…”

Section: Binary Dose Discriminationmentioning

confidence: 55%

Raman micro-spectroscopy analysis of human lens epithelial cells exposed to a low-dose-range of ionizing radiation

et al. 2018

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Recent findings in populations exposed to ionizing radiation (IR) indicate dose-related lens opacification occurs at much lower doses (<2 Gy) than indicated in radiation protection guidelines. As a result, research efforts are now being directed towards identifying early predictors of lens degeneration resulting in cataractogenesis. In this study, Raman micro-spectroscopy was used to investigate the effects of varying doses of radiation, ranging from 0.01 Gy to 5 Gy, on human lens epithelial (HLE) cells which were chemically fixed 24 h post-irradiation. Raman spectra were acquired from the nucleus and cytoplasm of the HLE cells. Spectra were collected from points in a 3 × 3 grid pattern and then averaged. The raw spectra were preprocessed and principal component analysis followed by linear discriminant analysis was used to discriminate between dose and control for 0.25, 0.5, 2, and 5 Gy. Using leave-one-out cross-validation accuracies of greater than 74% were attained for each dose/control combination. The ultra-low doses 0.01 and 0.05 Gy were included in an analysis of band intensities for Raman bands found to be significant in the linear discrimination, and an induced repair model survival curve was fit to a band-difference-ratio plot of this data, suggesting HLE cells undergo a nonlinear response to low-doses of IR. A survival curve was also fit to clonogenic assay data done on the irradiated HLE cells, showing a similar nonlinear response.

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“…These ideas are fiercely unpopular among those who wish to promote a threshold model of radiation protection because any possibility that radiation might cause any adverse low dose effects, means that a precautionary approach is likely to be retained when setting dose limits [ 21 , 22 , 23 , 24 ]. The reality is that low dose hypersensitivity exists [ 25 , 26 , 27 , 28 ] and non-targeted effects (discussed in the next section), can result in both “good” and “bad” effects [ 2 , 29 , 30 , 31 , 32 ]. The debate should not really be centered on whether low doses of radiation are good or bad but should be concerned with how systems deal with low doses of stressors and whether improved modelling or approaches such as adverse outcome pathway (AOP) analysis can improve our ability to understand and thus predict individual responses.…”

Section: Introduction To Low Dose and Non-targeted Radiobiologymentioning

confidence: 99%

Low Dose and Non-Targeted Radiation Effects in Environmental Protection and Medicine—A New Model Focusing on Electromagnetic Signaling

Mothersill

Cocchetto

Seymour

2022

IJMS

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The role of signalling in initiating and perpetuating effects triggered by deposition of ionising radiation energy in parts of a system is very clear. Less clear are the very early steps involved in converting energy to chemical and biological effects in non-targeted parts of the system. The paper aims to present a new model, which could aid our understanding of the role of low dose effects in determining ultimate disease outcomes. We propose a key role for electromagnetic signals resulting from physico-chemical processes such as excitation decay, and acoustic waves. These lead to the initiation of damage response pathways such as elevation of reactive oxygen species and membrane associated changes in key ion channels. Critically, these signalling pathways allow coordination of responses across system levels. For example, depending on how these perturbations are transduced, adverse or beneficial outcomes may predominate. We suggest that by appreciating the importance of signalling and communication between multiple levels of organisation, a unified theory could emerge. This would allow the development of models incorporating time, space and system level to position data in appropriate areas of a multidimensional domain. We propose the use of the term “infosome” to capture the nature of radiation-induced communication systems which include physical as well as chemical signals. We have named our model “the variable response model” or “VRM” which allows for multiple outcomes following exposure to low doses or to signals from low dose irradiated cells, tissues or organisms. We suggest that the use of both dose and infosome in radiation protection might open up new conceptual avenues that could allow intrinsic uncertainty to be embraced within a holistic protection framework.

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Radiobiological Response of Cervical Cancer Cell Line in Low Dose Region: Evidence of Low Dose Hypersensitivity (HRS) and Induced Radioresistance (IRR)

Cited by 5 publications

References 16 publications

Quantification of DNA double-strand break induced by radiation in cervix cancer cells: in vitro study

Quantification of DNA double-strand break induced by radiation in cervix cancer cells: in vitro study

Raman micro-spectroscopy analysis of human lens epithelial cells exposed to a low-dose-range of ionizing radiation

Low Dose and Non-Targeted Radiation Effects in Environmental Protection and Medicine—A New Model Focusing on Electromagnetic Signaling

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