P53 MUTATION DOES NOT CORRELATE WITH RADIOSENSITIVITY IN 24 HEAD AND NECK-CANCER CELL-LINES

The molecular basis of tumor response to therapeutic radiation is poor ly understood. Recent evidence suggests the p53 tumor suppressor gene may be involved in production of the G1 arrest seen following DNA dama ge by X-irradiation. It has further been proposed that tumor cells lac king the p53 checkpoint function are likely to be more sensitive to ce ll 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 surv iving 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 2 4 (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-Wh itney test). Furthermore, no association between radiosensitivity and mutational type, codon location, or predicted amino acid alteration wa s noted. Our data do not support the hypothesis that p53 gene alterati on predisposes tumor cells to increased cell killing via radiation.