title: Changes in G1-phase populations in human glioblastoma and neuroblastoma cell lines influence p66/Be neutron-induced micronucleus yield.
abstract: Some photon resistant tumours are sensitive to neutrons but no predictive methods exist which could identify such tumours. In a recent study addressing this clinically important issue, we demonstrated that relative biologic effectiveness (RBE) values for p(66)/Be neutrons estimated from micronucleus (MN) data correlate positively with RBE values obtained from conventional clonogenic survival data. However, not all photon-resistant cell lines showed high RBE values when the MN endpoint was used. Now, we examine how the functional status of the p53 tumour suppressor gene and radiation-induced changes in cell cycle phase populations may contribute to this discrepancy. No significant association was established between p53 status and MN yield for both photon and neutron irradiation. The data demonstrated that neutron-, but not photon-, induced MN yield is dependent on the intrinsic ability of cells to activate a G1-phase arrest. In cell lines of comparable photon sensitivity, those showing more extensive depletion of the G1 population express significantly more micronuclei per unit dose of neutrons. These results suggest that differences in cell cycle kinetics, and not the p53 status, may constitute an important factor in damage induction by high linear energy transfer (LET) irradiation and need to be considered when radiation toxicity in clinical radiobiology or radiation protection is assessed using damage endpoints.
authors.affiliation: Department of Radiation Oncology, Faculty of Health Sciences and Tygerberg Hospital, University of Stellenbosch, Tygerberg, South Africa. jakudugu@uhnres.utoronto.ca
authors.forename: John M
authors.initials: JM
authors.lastname: Akudugu
authors.forename: Anke
authors.initials: A
authors.lastname: Binder
authors.forename: Antonio
authors.initials: A
authors.lastname: Serafin
authors.forename: Jacobus
authors.initials: J
authors.lastname: Slabbert
authors.forename: Alf
authors.initials: A
authors.lastname: Giese
authors.forename: Lothar
authors.initials: L
authors.lastname: Böhm
mesh_terms: D001608:Beryllium / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D005434:Flow Cytometry; D016193:G1 Phase / Q000528:radiation effects*; D005909:Glioblastoma / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D018499:Linear Energy Transfer; D048629:Micronuclei, Chromosome-Defective / Q000528:radiation effects*; D015162:Micronucleus Tests; D009447:Neuroblastoma / Q000473:pathology / Q000532:radiotherapy*; D009502:Neutrons / Q000627:therapeutic use; D017785:Photons / Q000627:therapeutic use; D011836:Radiation Tolerance; D013997:Time Factors
chemical_list: D001608:Beryllium