Detection of individual differences in radiation-induced apoptosis of peripheral blood lymphocytes in normal individuals, ataxia telangiectasia homozygotes and heterozygotes, and breast cancer patients after radiotherapy.

2.50
Hdl Handle:
http://hdl.handle.net/10541/86199
Title:
Detection of individual differences in radiation-induced apoptosis of peripheral blood lymphocytes in normal individuals, ataxia telangiectasia homozygotes and heterozygotes, and breast cancer patients after radiotherapy.
Authors:
Barber, James B P; West, Catharine M L; Kiltie, Anne E; Roberts, Stephen A; Scott, David
Abstract:
Quantification of radiation-induced apoptosis in peripheral blood lymphocytes (PBLs) has been proposed as a possible screening test for cancer-prone individuals and also for the prediction of normal tissue responses after radiotherapy. We have used the TUNEL assay (terminal transferase nick-end labeling) 24 h after irradiation with 4 Gy at high dose rate to assess interindividual differences in radiation-induced apoptosis between (1) a panel of normal individuals, (2) ataxia telangiectasia (AT) homozygotes and heterozygotes, and (3) breast cancer patients who had received radiotherapy 8-13 years ago, including a number of patients who had suffered adverse responses to radiation. With this protocol, we show clear differences in radiation-induced apoptosis between individuals, and good reproducibility in the assay. In agreement with previous reports using EBV-transformed lymphoblasts, we show a very poor induction of apoptosis in AT homozygotes and a reduced level in AT heterozygotes compared to normal individuals. A similar reduced level compared to normal individuals was seen in the breast cancer patients. Despite a wide range of values in the breast cancer patients and good reproducibility on repeat samples, there was no correlation of rates of apoptosis with the severity of breast fibrosis, retraction or telangiectasia. The reduced rate of apoptosis observed in the breast cancer cases may be associated with genetic predisposition to breast cancer; however, we conclude that assays of lymphocyte apoptosis are unlikely to be of use in predicting normal tissue tolerance to radiotherapy.
Affiliation:
CRC Section of Molecular Genetics, Paterson Institute for Cancer Research, Christie CRC Research Centre, Manchester M20 9BX, United Kingdom.
Citation:
Detection of individual differences in radiation-induced apoptosis of peripheral blood lymphocytes in normal individuals, ataxia telangiectasia homozygotes and heterozygotes, and breast cancer patients after radiotherapy. 2000, 153 (5 Pt 1):570-8 Radiat. Res.
Journal:
Radiation Research
Issue Date:
May-2000
URI:
http://hdl.handle.net/10541/86199
DOI:
10.1667/0033-7587(2000)153[0570:DOIDIR]2.0.CO;2
PubMed ID:
10790278
Type:
Article
Language:
en
ISSN:
0033-7587
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorBarber, James B Pen
dc.contributor.authorWest, Catharine M Len
dc.contributor.authorKiltie, Anne Een
dc.contributor.authorRoberts, Stephen Aen
dc.contributor.authorScott, Daviden
dc.date.accessioned2009-11-13T16:30:45Z-
dc.date.available2009-11-13T16:30:45Z-
dc.date.issued2000-05-
dc.identifier.citationDetection of individual differences in radiation-induced apoptosis of peripheral blood lymphocytes in normal individuals, ataxia telangiectasia homozygotes and heterozygotes, and breast cancer patients after radiotherapy. 2000, 153 (5 Pt 1):570-8 Radiat. Res.en
dc.identifier.issn0033-7587-
dc.identifier.pmid10790278-
dc.identifier.doi10.1667/0033-7587(2000)153[0570:DOIDIR]2.0.CO;2-
dc.identifier.urihttp://hdl.handle.net/10541/86199-
dc.description.abstractQuantification of radiation-induced apoptosis in peripheral blood lymphocytes (PBLs) has been proposed as a possible screening test for cancer-prone individuals and also for the prediction of normal tissue responses after radiotherapy. We have used the TUNEL assay (terminal transferase nick-end labeling) 24 h after irradiation with 4 Gy at high dose rate to assess interindividual differences in radiation-induced apoptosis between (1) a panel of normal individuals, (2) ataxia telangiectasia (AT) homozygotes and heterozygotes, and (3) breast cancer patients who had received radiotherapy 8-13 years ago, including a number of patients who had suffered adverse responses to radiation. With this protocol, we show clear differences in radiation-induced apoptosis between individuals, and good reproducibility in the assay. In agreement with previous reports using EBV-transformed lymphoblasts, we show a very poor induction of apoptosis in AT homozygotes and a reduced level in AT heterozygotes compared to normal individuals. A similar reduced level compared to normal individuals was seen in the breast cancer patients. Despite a wide range of values in the breast cancer patients and good reproducibility on repeat samples, there was no correlation of rates of apoptosis with the severity of breast fibrosis, retraction or telangiectasia. The reduced rate of apoptosis observed in the breast cancer cases may be associated with genetic predisposition to breast cancer; however, we conclude that assays of lymphocyte apoptosis are unlikely to be of use in predicting normal tissue tolerance to radiotherapy.en
dc.language.isoenen
dc.subjectBreast Canceren
dc.subject.meshAdult-
dc.subject.meshApoptosis-
dc.subject.meshAtaxia Telangiectasia-
dc.subject.meshBreast Neoplasms-
dc.subject.meshCase-Control Studies-
dc.subject.meshCohort Studies-
dc.subject.meshFemale-
dc.subject.meshFlow Cytometry-
dc.subject.meshHeterozygote-
dc.subject.meshHomozygote-
dc.subject.meshHumans-
dc.subject.meshIn Situ Nick-End Labeling-
dc.subject.meshLight-
dc.subject.meshLymphocytes-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshReproducibility of Results-
dc.subject.meshScattering, Radiation-
dc.titleDetection of individual differences in radiation-induced apoptosis of peripheral blood lymphocytes in normal individuals, ataxia telangiectasia homozygotes and heterozygotes, and breast cancer patients after radiotherapy.en
dc.typeArticleen
dc.contributor.departmentCRC Section of Molecular Genetics, Paterson Institute for Cancer Research, Christie CRC Research Centre, Manchester M20 9BX, United Kingdom.en
dc.identifier.journalRadiation Researchen

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