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No defect in G1/S cell cycle arrest in irradiated Li-Fraumeni lymphoblastoid cell lines
K J Williams1, J Heighway, J M Birch
1CRC Department of Cancer Genetics, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
Abstract:
The radiation response of Epstein-Barr virus (EBV)-immortalised lymphoblastoid cell lines derive from Li-Fraumeni syndrome (LFS) and LFS-like individuals was investigated. Cells from all LFS and LFS-like cases showed an accumulation of p53 protein following 137Cs gamma-irradiation, which was associated with cell cycle arrest at the G1/S border. This response was indistinguishable from that seen in cells derived from normal individuals, and occurred in cases with missense mutations in the TP53 gene at codons 175, 180, 220 and 248 and also in two LFS-like individuals with no TP53 mutation. Previous studies using lymphocytes and fibroblasts from LFS individuals have demonstrated abnormal radiation responses in these cells. This suggest cell type specificity in the contribution of a mutant p53 protein to phenotype.