Radiation-induced G1 arrest is not defective in fibroblasts from Li-Fraumeni families without TP53 mutations

• Published in: British journal of cancer Vol. 79; no. 11-12; pp. 1657 - 1664
• Main Authors: BOYLE, J. M, GREAVES, M. J, CAMPLEJOHN, R. S, BIRCH, J. M, ROBERTS, S. A, VARLEY, J. M
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.04.1999
• Subjects: Alleles; Biological and medical sciences; Colony-Forming Units Assay; Fibroblasts - cytology; Fibroblasts - radiation effects; G1 Phase - radiation effects; Genetic Carrier Screening; Humans; Li-Fraumeni Syndrome - genetics; Li-Fraumeni Syndrome - pathology; Medical sciences; Mutation; Radiation therapy and radiosensitizing agent; Regular; Saccharomyces cerevisiae - genetics; Treatment with physical agents; Treatment. General aspects; Tumors; Human; Multiple; Radiosensitivity; Malignant tumor; Radiotherapy; In vitro; Genetic disease; Ionizing irradiation; G1 Phase; TP53 Gene; Li Fraumeni syndrome; Treatment; Cell cycle; Genetics; Fibroblast; Tumor suppressor gene
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6690265

Radiation-induced G1 arrest was studied in four classes of early passage skin fibroblasts comprising 12 normals, 12 heterozygous (mut/wt) TP53 mutation-carriers, two homozygous (mut/-) TP53 mutation-carriers and 16 strains from nine Li-Fraumeni syndrome or Li-Fraumeni-like families in which no TP53 mutation has been found, despite sequencing of all exons, exon-intron boundaries, 3' and 5' untranslated regions and promoter regions. In an assay of p53 allelic expression in yeast, cDNAs from these non-mutation strains behaved as wild-type p53. Using two different assays, we found G1 arrest was reduced in heterozygous strains with mis-sense mutations and one truncation mutation, when compared to the range established for the normal cells. Heterozygous strains with mutations at splice sites behaved like normal cells, whilst homozygous (mut/-) strains showed either extremely reduced, or no, arrest. Strains from all nine non-mutation families gave responses within the normal range. Exceptions to the previously reported inverse correlation between G1 arrest and clonogenic radiation resistance were observed, indicating that these phenotypes are not strictly interdependent.