Radiation and germline mutation at repeat sequences: Are we in the middle of a paradigm shift?

Authors
Citation
Ba. Bridges, Radiation and germline mutation at repeat sequences: Are we in the middle of a paradigm shift?, RADIAT RES, 156(5), 2001, pp. 631-641
Citations number
89
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Experimental Biology
Journal title
RADIATION RESEARCH
ISSN journal
0033-7587 → ACNP
Volume
156
Issue
5
Year of publication
2001
Part
2
Pages
631 - 641
Database
ISI
SICI code
0033-7587(200111)156:5<631:RAGMAR>2.0.ZU;2-G
Abstract
Two assumptions are commonly made in the estimation of genetic risk: (1) th at the seven specific loci in the mouse constitute a suitable basis for ext rapolation 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 reviewe d 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 alterat ions in them may have health consequences. Many of them are unstable, both spontaneously and after irradiation. The fact that changes in DNA repeat se quences can clearly arise as a result of radiation damage outside the seque nce concerned and the likely involvement of some sort of signal transductio n. process mean that the nature of the radiation dose response cannot be as sumed. While the time has not come to abandon the current paradigms, it wou ld seem sensible to invest more effort in exploring the induction of change s in repeat sequences after irradiation and the consequences of such change s for health. (C) 2001 by Radiation Research Society.