Chromosome Damage and Cell Proliferation Rates in In Vitro Irradiated Whole Blood as Markers of Late Radiation Toxicity After Radiation Therapy to the Prostate

Beaton, Lindsay A.; Ferrarotto, C.; Marro, Leonora; Samiee, S.; Malone, Shawn; Grimes, Scott; Malone, Kyle; Wilkins, Ruth

doi:10.1016/j.ijrobp.2012.09.026

Cited by 21 publications

(23 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous work with these patients (Beaton et al 2012) had identifi ed a correlation between unstable chromosome damage and the occurrence of late normal tissue side-eff ects. Specifi cally, using the classic dicentric chromosome assay (DCA), there was a signifi cant diff erence in the number of excess fragments per cell ( p Ͻ 0.0001) and in the fraction of cells in second metaphase ( p ϭ 0.0007), between the control group and the radiosensitive group.…”

Section: Discussionmentioning

confidence: 96%

“…While the FISH assay is more expensive as compared to the DCA and the measurement of proliferation rate (Beaton et al 2012), it would provide an additional test to strengthen the diagnosis of a patient ' s individual sensitivity. As well, the initial processing of the blood sample is similar to that of the DCA and could be performed simultaneously.…”

Section: Discussionmentioning

confidence: 99%

“…Th ese FISH results could be used in conjunction with other biomarkers identifi ed in earlier work (Beaton et al 2012) to identify radiosensitive patients prior to treatment with more statistical confi dence.…”

Section: Discussionmentioning

confidence: 99%

“…Previous research from our institutions indicated that unstable damage (dicentric chromosomes and excess acentric fragments) induced by high dose of in vitro irradiation, correlates with the onset of late normal tissue toxicity (Beaton et al 2012). Further research was carried out to investigate whether stable damage such as chromosome translocations would also be evidenced after a similar high dose of in vitro irradiation.…”

Section: Introductionmentioning

confidence: 99%

“…Beaton et al 2012), the patients were selected from an ongoing phase 3 clinical trial evaluating the optimal timing of Dose Escalated Radiation (76 Gy) and short course (6 months) Androgen Deprivation Th erapy for intermediate-risk prostate cancer (OTT0101, OHREB #2001014-01H). Prospective studies have confi rmed that dose escalated radiation using 3D conformal radiation and Intensity-Modulated Radiotherapy has a 5% or less toxicity.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Investigating chromosome damage using fluorescentin situhybridization to identify biomarkers of radiosensitivity in prostate cancer patients

Beaton¹,

Marro²,

Samiee³

et al. 2013

International Journal of Radiation Biology

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Investigating chromosome damage using fluorescentin situhybridization to identify biomarkers of radiosensitivity in prostate cancer patients

Beaton¹,

Marro²,

Samiee³

et al. 2013

International Journal of Radiation Biology

Self Cite

View full text Add to dashboard Cite

show abstract

Raman spectroscopy of lymphocytes for the identification of prostate cancer patients with late radiation toxicity following radiotherapy

Cullen

Bryant

Maguire

et al. 2020

Transl Biophotonics

View full text Add to dashboard Cite

The success of radiotherapy in tumour control depends on the total dose given. However, the tolerance of the normal tissues surrounding the tumour limits this dose. It is not known why some patients develop radiation toxicity and, currently, it is not possible to predict before treatment which patients will experience adverse effects. Thus, there is an unmet clinical need for a new test to identify patients at risk of radiation toxicity. Here, we report a new approach based on Raman spectroscopy. Blood samples were collected from 42 patients who had undergone radiotherapy for prostate cancer and had shown either severe or no/minimal late radiation toxicity in follow up. Radiation response was assessed following in vitro irradiation using Raman spectroscopy in addition to the G2 chromosomal radiosensitivity assay and the γH2AX DNA damage assay. A partial least squares discriminant analysis model was developed to classify patients using known radiation toxicity scores. A sensitivity of 95%, specificity of 92% and overall accuracy of 93% was achieved. In the future, this technology may have potential to lead to individualized patient radiotherapy by identifying which patients are at risk of radiation toxicity.

show abstract

DNA double-strand break repair and induction of apoptosis in ex vivo irradiated blood lymphocytes in relation to late normal tissue reactions following breast radiotherapy

Chua

Horn

Somaiah

et al. 2014

Radiat Environ Biophys

View full text Add to dashboard Cite

This study aimed to test whether induction of apoptosis following ex vivo X-irradiation of unstimulated blood lymphocytes correlated with clinical radiosensitivity and DNA double-strand break (DSB) repair in breast radiotherapy patients and healthy volunteers. Using small molecule inhibitors, the relationship between DSB repair and radiation-induced apoptosis was examined. Sixteen breast cancer patients with minimal (controls, n = 8) or extremely marked late radiation-induced change (cases, n = 8) and eight healthy volunteers were selected. DSBs were quantified by γH2AX/53BP1 immunofluorescence, and apoptosis was measured using a fluorogenic inhibitor of caspases assay. Mean γH2AX/53BP1 focus levels 24 h after exposure to 4 Gy were higher in cases (12.7 foci per cell) than in controls (10.3 foci per cell, p = 0.002). In contrast, the mean apoptotic fraction 48 h after 8 Gy was comparable, 37.2 % in cases and 34.7 % in controls (p = 0.442). Residual focus and apoptosis levels were not correlated within individuals (Spearman's R = -0.0059, p = 0.785). However, cells treated with DNA-PK inhibitor Nu7441 had higher focus and apoptosis levels 48 h after 1 Gy compared to mock-treated cells, suggesting that apoptosis induction following irradiation is modulated by DSB repair. This effect required functional ATM since cells treated simultaneously with Nu7441 and the ATM inhibitor Ku55933 were resistant to apoptosis despite high levels of residual foci. One clinical case displayed an impaired DNA-PK-dependent end-joining cellular phenotype. In summary, clinical radiosensitivity may be associated with impaired DSB repair in some patients. Although pharmaceutical inhibition of ATM and DNA-PK affected apoptosis induction and DSB repair, no association was observed between apoptosis and residual focus levels in patients and volunteers.

show abstract

Chromosome Damage and Cell Proliferation Rates in In Vitro Irradiated Whole Blood as Markers of Late Radiation Toxicity After Radiation Therapy to the Prostate

Cited by 21 publications

References 19 publications

Investigating chromosome damage using fluorescentin situhybridization to identify biomarkers of radiosensitivity in prostate cancer patients

Investigating chromosome damage using fluorescentin situhybridization to identify biomarkers of radiosensitivity in prostate cancer patients

Raman spectroscopy of lymphocytes for the identification of prostate cancer patients with late radiation toxicity following radiotherapy

DNA double-strand break repair and induction of apoptosis in ex vivo irradiated blood lymphocytes in relation to late normal tissue reactions following breast radiotherapy

Contact Info

Product

Resources

About