title: p53 mutation does not correlate with radiosensitivity in 24 head and neck cancer cell lines.
abstract: The molecular basis of tumor response to therapeutic radiation is poorly understood. Recent evidence suggests the p53 tumor suppressor gene may be involved in production of the G1 arrest seen following DNA damage by X-irradiation. It has further been proposed that tumor cells lacking the p53 checkpoint function are likely to be more sensitive to cell killing by X-irradiation because these cells enter S phase despite unrepaired DNA damage. We tested the hypothesis that tumor cells with p53 mutations are more radiosensitive by correlating the in vitro surviving fraction at 2 Gy with the mutational status of 24 head and neck squamous cell cancer cell lines. p53 mutations were present in 15 of 24 (63%) of tumors; all were homozygous changes occurring within exons 5-9. The surviving fraction at 2 Gy for the group with mutations was 0.568 compared to 0.507 for tumors without mutations (P = 0.28, Mann-Whitney test). Furthermore, no association between radiosensitivity and mutational type, codon location, or predicted amino acid alteration was noted. Our data do not support the hypothesis that p53 gene alteration predisposes tumor cells to increased cell killing via radiation.
authors.affiliation: Department of Radiation and Cellular Oncology, University of Chicago Hospitals, Illinois 60637.
authors.forename: D G
authors.initials: DG
authors.lastname: Brachman
authors.forename: M
authors.initials: M
authors.lastname: Beckett
authors.forename: D
authors.initials: D
authors.lastname: Graves
authors.forename: D
authors.initials: D
authors.lastname: Haraf
authors.forename: E
authors.initials: E
authors.lastname: Vokes
authors.forename: R R
authors.initials: RR
authors.lastname: Weichselbaum
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000532:radiotherapy; D002470:Cell Survival / Q000528:radiation effects; D004260:DNA Repair; D016193:G1 Phase; D016158:Genes, p53 / Q000235:genetics* / Q000502:physiology; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000532:radiotherapy; D006801:Humans; D009154:Mutation; D011836:Radiation Tolerance; D016196:S Phase; D014407:Tumor Cells, Cultured