Radiation and Germline Mutation at Repeat Sequences: Are We in the Middle of a Paradigm Shift?
- 1 November 2001
- journal article
- Published by Radiation Research Society in Radiation Research
- Vol. 156 (5) , 631-641
- https://doi.org/10.1667/0033-7587(2001)156[0631:ragmar]2.0.co;2
Abstract
Two assumptions are commonly made in the estimation of genetic risk: (1) that the seven specific loci in the mouse constitute a suitable basis for extrapolation to genetic disease in humans, and (2) that mutations are induced by radiation damage (energy-loss events leading to double-stranded damage) occurring within the gene and are induced linearly with dose, at least at low doses. Recent evidence on the mutability of repeat sequences is reviewed that suggests that neither of these assumptions is as well founded as we like to think. Repeat sequences are common in the human genome, and alterations in them may have health consequences. Many of them are unstable, both spontaneously and after irradiation. The fact that changes in DNA repeat sequences can clearly arise as a result of radiation damage outside the sequence concerned and the likely involvement of some sort of signal transduction process mean that the nature of the radiation dose response cannot be assumed. While the time has not come to abandon the current paradigms, it would seem sensible to invest more effort in exploring the induction of changes in repeat sequences after irradiation and the consequences of such changes for health.Keywords
This publication has 75 references indexed in Scilit:
- Primary Myopathy and Accumulation of PrPSc-Like Molecules in Peripheral Tissues of Transgenic Mice Expressing a Prion Protein Insertional MutationNeurobiology of Disease, 2001
- Ionizing radiation and genetic risks: IX. Estimates of the frequencies of mendelian diseases and spontaneous mutation rates in human populations: a 1998 perspectiveMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 1998
- In vitro fertilization rate of mouse oocytes with spermatozoa from the F1 offspring of males irradiated with 1.0 Gy 137Cs γ-raysMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 1997
- Effects of radiation on childrenNature, 1996
- Instability at the H-ras Minisatellite Is Associated with the Spontaneous Abortion of the EmbryoBiochemical and Biophysical Research Communications, 1995
- Analysis of restriction enzyme-induced chromosome aberrations in the interstitial telomeric repeat sequences of CHO and CHE cells by FISHMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 1994
- Radiation Induction of Germline Mutation at a Hypervariable Mouse Minisatellite LocusInternational Journal of Radiation Biology, 1994
- Chromosomal instabilityNature, 1992
- Direct Molecular Identification of the Mouse Pink-Eyed Unstable Mutation by Genome ScanningScience, 1991
- X-ray- and chemically induced germ-line mutation causing phenotypical anomalies in miceMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 1988