title: Multicentric investigation of ionising radiation-induced cell death as a predictive parameter of individual radiosensitivity.
abstract: In the present study, the predictive value of ionising radiation (IR)-induced cell death was tested in peripheral blood lymphocytes (PBLs) and their corresponding Epstein-Barr virus-transformed lymphoblastoid cell lines (LCLs) in an interlaboratory comparison. PBLs and their corresponding LCLs were derived from 15 tumour patients, that were considered clinically radiosensitive based on acute side-effects, and matched controls. Upon coding of the samples, radiosensitivity of the matched pairs was analysed in parallel in three different laboratories by assessing radiation-induced apoptotic and necrotic cell death using annexin V. All participating laboratories detected a dose-dependent increase of apoptosis and necrosis in the individual samples, to a very similar extent. However, comparing the mean values of apoptotic and necrotic levels derived from PBLs of the radiosensitive cohort with the mean values of the control cohort did not reveal a significant difference. Furthermore, within 15 matched pairs, no sample was unambiguously and independently identified by all three participating laboratories to demonstrate in vitro hypersensitivity that matched the clinical hypersensitivity. As has been reported previously, apoptotic and necrotic cell death is barely detectable in immortalised LCL derivatives using low doses of IR. Concomitantly, the differences in apoptosis or necrosis levels found in primary cells of different individuals were not observed in the corresponding LCL derivatives. All participating laboratories concordantly reasoned that, with the methods applied here, IR-induced cell death in PBLs is unsuitable to unequivocally predict the individual clinical radiosensitivity of cancer patients. Furthermore, LCLs do not reflect the physiological properties of the corresponding primary blood lymphocytes with regard to IR-induced cell death. Their value to predict clinical radiosensitivity is thus highly questionable.
authors.affiliation: Department of Radiotherapy, University Hospital of Münster, Albert-Schweitzer-Strasse 33, 48149 Münster, Germany. greveb@uni-muenster.de
authors.forename: Burkhard
authors.initials: B
authors.lastname: Greve
authors.forename: Kristin
authors.initials: K
authors.lastname: Dreffke
authors.forename: Astrid
authors.initials: A
authors.lastname: Rickinger
authors.forename: Stefan
authors.initials: S
authors.lastname: Könemann
authors.forename: Eberhard
authors.initials: E
authors.lastname: Fritz
authors.forename: Friederike
authors.initials: F
authors.lastname: Eckardt-Schupp
authors.forename: Susanne
authors.initials: S
authors.lastname: Amler
authors.forename: Cristina
authors.initials: C
authors.lastname: Sauerland
authors.forename: Herbert
authors.initials: H
authors.lastname: Braselmann
authors.forename: Wiebke
authors.initials: W
authors.lastname: Sauter
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Peter
authors.initials: P
authors.lastname: Schmezer
authors.forename: Maria
authors.initials: M
authors.lastname: Gomolka
authors.forename: Normann
authors.initials: N
authors.lastname: Willich
authors.forename: Tobias
authors.initials: T
authors.lastname: Bölling
mesh_terms: D000368:Aged; D016923:Cell Death / Q000528:radiation effects; D002460:Cell Line; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008214:Lymphocytes / Q000473:pathology / Q000528:radiation effects; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D011836:Radiation Tolerance / Q000528:radiation effects*; D011839:Radiation, Ionizing; D011878:Radiotherapy / Q000009:adverse effects; D013997:Time Factors