Abstract
The TK6 lymphoblastoid cell line is known to be mismatch repair (MMR) and p53 proficient. Deficiency in MMR results in a mutator phenotype characterized by microsatellite instability (MSI) and increased hprt mutant frequency (MF). Increased hprt MF is also a biomarker of effect for exposure to ionizing radiation. In order to test if a mutator phenotype could be induced by low doses of gamma ionizing radiation, an hprt cloning assay and a MSI investigation were performed after radiation exposure. The spontaneous MF was 1.6 x 10-6. The groups exposed to 0.2, 0.5 and 1.0 Gy had hprt MFs of 2.3, 3.3 and 2.2 x 10-6, respectively. The spontaneous MSI frequency per allele in non-selected cells was 5.4 x 10-3, as evidenced at the loci D11S35, nm23-H1, D8S135 and p53. MSI frequencies in the groups exposed to 0.2, 0.5 and 1.0 Gy were found to be < 4.7, < 7.7 and < 12 x 10-3, respectively. The frequencies of hprt mutants and MSI found in this study suggest that low doses of ionizing radiation increase hprt mutant frequency without triggering the mutator phenotype pathway.
Highlights
TK6 is a lymphoblastoid cell line heterozygous at the thymidine kinase locus (Skopek et al, 1978) that has been characterized by the karyotype 47,XY,+13,14q+,21p+ (Grosovsky et al, 1996)
MMR deficiency results in mutator phenotype associated with microsatellite instability and elevated mutation rates at the hprt locus (Aquilina and Bignami, 2001)
Hprt mutant selection is a rare event measured per ~10-6 assayed cells, in which it is assumed that only one mutant clone gives raise to each positive colony (Albertini et al, 2000)
Summary
TK6 is a lymphoblastoid cell line heterozygous at the thymidine kinase locus (Skopek et al, 1978) that has been characterized by the karyotype 47,XY,+13,14q+,21p+ (Grosovsky et al, 1996). We used the hprt cloning assay and microsatellite analysis to investigate if low doses of gamma ionizing radiation can induce a persistent genetic instability
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