Relationship between in vitro chromosomal radiosensitivity of peripheral blood lymphocytes and the expression of normal tissue damage following radiotherapy for breast cancer.

2.50
Hdl Handle:
http://hdl.handle.net/10541/86213
Title:
Relationship between in vitro chromosomal radiosensitivity of peripheral blood lymphocytes and the expression of normal tissue damage following radiotherapy for breast cancer.
Authors:
Barber, James B P; Burrill, Wayne; Spreadborough, Anne R; Levine, Edward; Warren, Coleen; Kiltie, Anne E; Roberts, Stephen A; Scott, David
Abstract:
BACKGROUND AND PURPOSE: There is a need for rapid and reliable tests for the prediction of normal tissue responses to radiotherapy, as this could lead to individualization of patient radiotherapy schedules and thus improvements in the therapeutic ratio. Because the use of cultured fibroblasts is too slow to be practicable in a clinical setting, we evaluated the predictive role of assays of lymphocyte chromosomal radiosensitivity in patients having radiotherapy for breast cancer. MATERIALS AND METHODS: Radiosensitivity was assessed using a micronucleus (MN) assay at high dose rate (HDR) and low dose rate (LDR) on lymphocytes irradiated in the G(0) phase of the cell cycle (Scott D, Barber JB, Levine EL, Burril W, Roberts SA. Radiation-induced micronucleus induction in lymphocytes identifies a frequency of radiosensitive cases among breast cancer patients: a test for predispostion? Br. J. Cancer 1998;77;614-620) and an assay of G(2) phase chromatid radiosensitivity ('G(2) assay') (Scott D, Spreadborough A, Levine E, Roberts SA. Genetic predisposition in breast cancer. Lancet 1994; 344: 1444). In a study of acute reactions, blood samples were taken from breast cancer patients before the start of radiotherapy, and the skin reaction documented. 116 patients were tested with the HDR MN assay, 73 with the LDR MN assay and 123 with the G(2) assay. In a study of late reactions, samples were taken from a series of breast cancer patients 8-14 years after radiotherapy and the patients assessed for the severity of late effects according to the'LENT SOMA' scales. 47 were tested with the HDR assay, 26 with the LDR assay and 19 with the G(2) assay. For each clinical endpoint, patients were classified as being normal reactors or 'highly radiosensitive patients' (HR patients (Burnet NG. Johansen J, Turesson I, Nyman J. Describing patients' normal tissue reactions: Concerning the possiblity of individualising radiotherapy dose presciptions based on potential predictive assays of normal tissue radiosensitivity. Int. J. Cancer 1998;79:606-613)). RESULTS: The HR patients could be identified in some of the assays. For example, for acute skin reactions, 9/123 patients were judged as HR; they had significantly higher G(2) scores than normal reactors (P=0.004). For the late reactions, the mean HDR MN scores were higher for the 4/47 patients who had severe telangiectasia (P=0.042) and the 8/47 patients had severe fibrosis (P=0.055). However, there were no trends towards increased chromosomal radiosensitivity with the micronucleus scores at HDR or LDR, or with G(2) chromosomal radiosensitivity. CONCLUSIONS: While these results support the concept of using lymphocytes to detect elevated sensitivity to radiotherapy (as an alternative to fibroblasts), these assays are unlikely to be of assistance for the prediction of normal tissue effects in the clinic in their present form.
Affiliation:
CRC Sections of Molecular Genetics, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
Citation:
Relationship between in vitro chromosomal radiosensitivity of peripheral blood lymphocytes and the expression of normal tissue damage following radiotherapy for breast cancer. 2000, 55 (2):179-86 Radiother Oncol
Journal:
Radiotherapy and Oncology
Issue Date:
May-2000
URI:
http://hdl.handle.net/10541/86213
DOI:
10.1016/S0167-8140(99)00158-9
PubMed ID:
10799730
Type:
Article
Language:
en
ISSN:
0167-8140
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorBarber, James B Pen
dc.contributor.authorBurrill, Wayneen
dc.contributor.authorSpreadborough, Anne Ren
dc.contributor.authorLevine, Edwarden
dc.contributor.authorWarren, Coleenen
dc.contributor.authorKiltie, Anne Een
dc.contributor.authorRoberts, Stephen Aen
dc.contributor.authorScott, Daviden
dc.date.accessioned2009-11-13T16:20:09Z-
dc.date.available2009-11-13T16:20:09Z-
dc.date.issued2000-05-
dc.identifier.citationRelationship between in vitro chromosomal radiosensitivity of peripheral blood lymphocytes and the expression of normal tissue damage following radiotherapy for breast cancer. 2000, 55 (2):179-86 Radiother Oncolen
dc.identifier.issn0167-8140-
dc.identifier.pmid10799730-
dc.identifier.doi10.1016/S0167-8140(99)00158-9-
dc.identifier.urihttp://hdl.handle.net/10541/86213-
dc.description.abstractBACKGROUND AND PURPOSE: There is a need for rapid and reliable tests for the prediction of normal tissue responses to radiotherapy, as this could lead to individualization of patient radiotherapy schedules and thus improvements in the therapeutic ratio. Because the use of cultured fibroblasts is too slow to be practicable in a clinical setting, we evaluated the predictive role of assays of lymphocyte chromosomal radiosensitivity in patients having radiotherapy for breast cancer. MATERIALS AND METHODS: Radiosensitivity was assessed using a micronucleus (MN) assay at high dose rate (HDR) and low dose rate (LDR) on lymphocytes irradiated in the G(0) phase of the cell cycle (Scott D, Barber JB, Levine EL, Burril W, Roberts SA. Radiation-induced micronucleus induction in lymphocytes identifies a frequency of radiosensitive cases among breast cancer patients: a test for predispostion? Br. J. Cancer 1998;77;614-620) and an assay of G(2) phase chromatid radiosensitivity ('G(2) assay') (Scott D, Spreadborough A, Levine E, Roberts SA. Genetic predisposition in breast cancer. Lancet 1994; 344: 1444). In a study of acute reactions, blood samples were taken from breast cancer patients before the start of radiotherapy, and the skin reaction documented. 116 patients were tested with the HDR MN assay, 73 with the LDR MN assay and 123 with the G(2) assay. In a study of late reactions, samples were taken from a series of breast cancer patients 8-14 years after radiotherapy and the patients assessed for the severity of late effects according to the'LENT SOMA' scales. 47 were tested with the HDR assay, 26 with the LDR assay and 19 with the G(2) assay. For each clinical endpoint, patients were classified as being normal reactors or 'highly radiosensitive patients' (HR patients (Burnet NG. Johansen J, Turesson I, Nyman J. Describing patients' normal tissue reactions: Concerning the possiblity of individualising radiotherapy dose presciptions based on potential predictive assays of normal tissue radiosensitivity. Int. J. Cancer 1998;79:606-613)). RESULTS: The HR patients could be identified in some of the assays. For example, for acute skin reactions, 9/123 patients were judged as HR; they had significantly higher G(2) scores than normal reactors (P=0.004). For the late reactions, the mean HDR MN scores were higher for the 4/47 patients who had severe telangiectasia (P=0.042) and the 8/47 patients had severe fibrosis (P=0.055). However, there were no trends towards increased chromosomal radiosensitivity with the micronucleus scores at HDR or LDR, or with G(2) chromosomal radiosensitivity. CONCLUSIONS: While these results support the concept of using lymphocytes to detect elevated sensitivity to radiotherapy (as an alternative to fibroblasts), these assays are unlikely to be of assistance for the prediction of normal tissue effects in the clinic in their present form.en
dc.language.isoenen
dc.subjectBreast Canceren
dc.subjectTumour Suppressor Proteinsen
dc.subject.meshAdult-
dc.subject.meshAge Factors-
dc.subject.meshAged-
dc.subject.meshBreast Neoplasms-
dc.subject.meshCell Cycle Proteins-
dc.subject.meshChromosomes, Human-
dc.subject.meshDNA-Binding Proteins-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshLymphocytes-
dc.subject.meshMicronucleus Tests-
dc.subject.meshMiddle Aged-
dc.subject.meshProtein-Serine-Threonine Kinases-
dc.subject.meshRadiation Tolerance-
dc.subject.meshRadiotherapy-
dc.subject.meshTumor Suppressor Proteins-
dc.titleRelationship between in vitro chromosomal radiosensitivity of peripheral blood lymphocytes and the expression of normal tissue damage following radiotherapy for breast cancer.en
dc.typeArticleen
dc.contributor.departmentCRC Sections of Molecular Genetics, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.en
dc.identifier.journalRadiotherapy and Oncologyen
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