Radiation-induced G(1) arrest is not defective in fibroblasts from Li-Fraumeni families without TP53 mutations

Radiation-induced G(1) arrest was studied in four classes of early passage skin fibroblasts comprising 12 normals, 12 heterozygous (mut/wt) TP53 mutat ion-carriers, two homozygous (mut/-) TP53 mutation-carriers and 16 strains from nine Li-Fraumeni syndrome or Li-Fraumeni-like families in which no TP5 3 mutation has been found, despite sequencing of all exons, exon-intron bou ndaries, 3' and 5' untranslated regions and promoter regions. In an assay o f p53 allelic expression in yeast, cDNAs from these non-mutation strains be haved as wild-type p53. Using two different assays, we found G(1) arrest wa s reduced in heterozygous strains with mis-sense mutations and one truncati on mutation, when compared to the range established for the normal cells. H eterozygous strains with mutations at splice sites behaved like normal cell s, 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 correlatio n between G(1) arrest and clonogenic radiation resistance were observed, in dicating that these phenotypes are not strictly interdependent.