Prediction of DNA damage and G2 chromosomal radio-sensitivity ex vivo in peripheral blood mononuclear cells with label-free Raman micro-spectroscopy

Meade, Aidan D.; Maguire, Adrian; Bryant, Jane; Cullen, D. Kacy; Medipally, Dinesh; White, Lisa M.; McClean, Brendan; Shields, Laura; Armstrong, John G.; Dunne, Mary; Noone, Emma; Bradshaw, Shirley; Finn, Marie; Shannon, Aoife M.; Howe, Orla; Lyng, Fiona M.

doi:10.1080/09553002.2018.1451006

Cited by 16 publications

(14 citation statements)

References 54 publications

(67 reference statements)

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“…In contrast, for 0.5 Gy the mean radiation-induced G2 scores exceeded the 90th percentile radiosensitivity cut-off of 152 abs/100 meta for both baseline (167.5 abs/100 meta) and ADT (162.6) compared to the healthy control cohort (122.6 abs/100 meta). It is well reported in the literature that 0.5 Gy IR is the most radiosensitive dose at G2 phase of the cell cycle due to checkpoint inefficacy [ 33 , 34 ], and prostate cancer patients exhibit elevated G2 radiosensitivity compared to healthy control donors at this dose [ 28 , 30 , 32 ].…”

Section: Resultsmentioning

confidence: 99%

“…This bioassay first described in irradiated cells by Parshad and colleagues [ 24 , 25 ] is now a well-known cytogenetic assay and therefore a biomarker for cellular radiosensitivity [ 26 ]. The assay is well-established and optimised at our own laboratory for predicting cellular radiosensitivity in blood samples obtained from many individuals in various cancer and healthy cohorts [ 27 , 28 , 29 , 30 , 31 ]. Herein, we report the potential of CDKN1, FDXR, SESN1 and PCNA packaged as a 4-gene signature as a potential radiosensitivity biomarker and validated using the G2 chromosomal radiosensitivity profile of individual samples of both the prostate cancer and healthy donor cohort exposed to low doses of IR.…”

Section: Introductionmentioning

confidence: 99%

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A 4-Gene Signature of CDKN1, FDXR, SESN1 and PCNA Radiation Biomarkers for Prediction of Patient Radiosensitivity

Howe

White

Cullen

et al. 2021

IJMS

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The quest for the discovery and validation of radiosensitivity biomarkers is ongoing and while conventional bioassays are well established as biomarkers, molecular advances have unveiled new emerging biomarkers. Herein, we present the validation of a new 4-gene signature panel of CDKN1, FDXR, SESN1 and PCNA previously reported to be radiation-responsive genes, using the conventional G2 chromosomal radiosensitivity assay. Radiation-induced G2 chromosomal radiosensitivity at 0.05 Gy and 0.5 Gy IR is presented for a healthy control (n = 45) and a prostate cancer (n = 14) donor cohort. For the prostate cancer cohort, data from two sampling time points (baseline and Androgen Deprivation Therapy (ADT)) is provided, and a significant difference (p > 0.001) between 0.05 Gy and 0.5 Gy was evident for all donor cohorts. Selected donor samples from each cohort also exposed to 0.05 Gy and 0.5 Gy IR were analysed for relative gene expression of the 4-gene signature. In the healthy donor cohort, there was a significant difference in gene expression between IR dose for CDKN1, FXDR and SESN1 but not PCNA and no significant difference found between all prostate cancer donors, unless they were classified as radiation-induced G2 chromosomal radiosensitive. Interestingly, ADT had an effect on radiation response for some donors highlighting intra-individual heterogeneity of prostate cancer donors.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A 4-Gene Signature of CDKN1, FDXR, SESN1 and PCNA Radiation Biomarkers for Prediction of Patient Radiosensitivity

Howe

White

Cullen

et al. 2021

IJMS

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“…Various studies are devoted at investigating the fixation effects on the Raman spectra of cells [28,29]. In particular, Meade et al showed that a fixation procedure with a low concentration of paraformaldehyde (3.7%) provides the best results and this procedure has been used in many recent studies [19,20,25,26,30,31].…”

Section: Methodsmentioning

confidence: 99%

Multivariate Analysis of Difference Raman Spectra of the Irradiated Nucleus and Cytoplasm Region of SH-SY5Y Human Neuroblastoma Cells

Delfino

Ricciardi

Manti

et al. 2019

Sensors

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Previous works showed that spatially resolved Raman spectra of cytoplasm and nucleus region of single cells exposed to X-rays evidence different features. The present work aims to introduce a new approach to profit from these differences to deeper investigate X-ray irradiation effects on single SH-SY5Y human neuroblastoma cells. For this aim, Raman micro-spectroscopy was performed in vitro on single cells after irradiation by graded X-ray doses (2, 4, 6, 8 Gy). Spectra from nucleus and cytoplasm regions were selectively acquired. The examination by interval Principal Component Analysis (i-PCA) of the difference spectra obtained by subtracting each cytoplasm-related spectrum from the corresponding one detected at the nucleus enabled us to reveal the subtle modifications of Raman features specific of different spatial cell regions. They were discussed in terms of effects induced by X-ray irradiation on DNA/RNA, lipids, and proteins. The proposed approach enabled us to evidence some features not outlined in previous investigations.

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“…Sophisticated applications of the technique for diagnosis of diseases including cancer [13,23,30,37,52] are now well established while novel applications to monitoring diabetes [39], detection of hyperbilirubinaemia [68], and observation of changes to the cervix during pregnancy [51] have emerged. In addition the sensitivity of Raman spectroscopy to biological effects occuring due to radiation exposure [43], radiotherapy [44] and chemotherapy [49] has also been demobstrated.…”

Section: Application Of Raman Spectroscopy In Identification and Classification Of Immune Cellsmentioning

confidence: 99%

A review of applications of Raman spectroscopy in immunology

Chaudhary

Wynne

Meade

2020

BSI

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Vibrational spectroscopic techniques have recently gained increasing clinical importance as non-invasive, rapid and inexpensive methods to obtain information on the content of biological samples. For some time Raman spectroscopy has been involved in preclinical applications, mainly in the cancer space, with evolving applications towards new horizons in the dermatology and companion diagnostics arena. It is attractive as an analytical technique due to its exquisite sensitivity, labelfree operation and low water detectivity such that in-vivo applications are possible. In cytometry, Raman spectroscopy has been applied to the analysis of single cells providing a label-free alternative to cell classification approaches in the laboratory. In this review we collate in-vitro, ex-vivo and in-vivo examples of research using Raman spectroscopy for the detection, quantification and analysis of immune signaling at the cellular level. While cancer biology has recently focussed on the role of immunological signals in the development of the disease, it is timely to examine these applications as research in this space evolves.

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Prediction of DNA damage and G2 chromosomal radio-sensitivity ex vivo in peripheral blood mononuclear cells with label-free Raman micro-spectroscopy

Abstract: Raman spectroscopy of PBMCs represents a label-free approach for prediction of DNA damage levels for either prospective or retrospective analysis.

Cited by 16 publications

References 54 publications

A 4-Gene Signature of CDKN1, FDXR, SESN1 and PCNA Radiation Biomarkers for Prediction of Patient Radiosensitivity

A 4-Gene Signature of CDKN1, FDXR, SESN1 and PCNA Radiation Biomarkers for Prediction of Patient Radiosensitivity

Multivariate Analysis of Difference Raman Spectra of the Irradiated Nucleus and Cytoplasm Region of SH-SY5Y Human Neuroblastoma Cells

A review of applications of Raman spectroscopy in immunology

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