Published June 20, 2011 | Version v1
Miscellaneous Open

Towards new biological dosimetry approaches

Description

Ionizing radiation (IR) is a ubiquitous environmental hazard and a well-known carcinogen. In general, exposures are low but accidents and incidents have led to significant exposures. The response to any radiation accident or incident involving actual or potential IR exposure requires accurate and rapid assessment of the doses received by individuals. This is required for initial 'triage' of exposed individuals, followed by more accurate assessment of doses in those exposed, to determine the most appropriate approach to treatment. Biological dosimetry, based on the scoring of chromosomal abnormalities - especially dicentric chromosomes - in peripheral blood lymphocytes, plays a key role. The dicentric assay is accurate and sensitive; however, it is a labor-intensive assay (>2 days from sampling to initial results), and it has a limited sample capacity available for mass screening following an accident or incident. Recently, many attempts have been made to improve dosimetry using different end-points. Different cytogenetic techniques have been proposed. Other techniques have shown some potential, and studies were performed on protein biomarkers such as histone phosphorylation (γ-H2AX) and telomere length quantification. In this study, we have established the dose response curve between the total intensity of γ-H2AX foci, and validated these results with conventional techniques. Similarly, we have demonstrated the dose response curve between telomere length and in vitro irradiation. This study has identified potential biomarkers (γ-H2AX and telomere length) of radiation exposure. This study must be validated further in different donors and studied in a wide range of doses, especially in very low doses. These two biomarkers can be useful in the progression of knowledge in the effect of low dose exposure. (author)

Abstract (French)

L'etendue du champ d'application des radiations ionisantes dans la vie quotidienne (industrielle, medicale et professionnelle) oblige la communaute scientifique a definir des normes de radioprotection et a developper des outils de surveillance et d'estimation de dose en cas d'accident. La mise en place de projets de recherche de nouvelle methodes de dosimetrie biologique ou de tri des populations exposees aux radiations ionisantes, par l'identification de marqueurs plus fiables et plus precis, temoigne de l'importance de ce probleme majeur. C'est dans cette optique que le Laboratoire de Radiologie Oncologie (LRO) etudie la quantification de l'intensite γH2AX ainsi que de la taille des telomeres en reponse a des radiations ionisantes. Notre etude consiste a quantifier le signal de γH2AX et le signal telomerique apres marquage par immunofluorescence et immunofluorescence par hybridation in situ (FISH) respectivement, sur des lymphocytes circulants preleve chez un donneur sain et irradies a differents doses (2 et 4 Gy). Une validation a ete effectuee par rapport a la technique de reference dite 'Gold Standard', qui denombre les aberrations chromosomiques instables, et a la technique de denombrement des aberrations stables a l'aide du Multi-FISH. Ces deux techniques ne necessitent pas de culture cellulaire ni de preparation de metaphases. Le resultat le plus important de cette etude est l'etablissement d'une courbe dose effet entre l'intensite de fluorescence de signal γH2AX et les doses absorbees. Ce signal depend de la dose mais egalement du temps passe apres l'irradiation avec une cinetique de disparition rapide de ce signal. C'est une technique de dosimetrie biologique ou de tri qui pourrait etre interessante dans les etudes organisees ou en sachant le temps passe apres l'irradiation. La validation de la quantification des telomeres comme technique de dosimetrie biologique au cours de ce travail merite plus d'investigation. Cette etude ouvre un nouveau champ dans l'application de la dosimetrie biologique avec l'introduction du signal γH2AX et des telomeres dans la perspective d'une etude de larges populations. (auteur)

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Additional details

Additional titles

Original title (French)
Vers de nouvelles approches de dosimetrie biologique

Publishing Information

Imprint Pagination
30 p.
Report number
INIS-FR--23-1094

Optional Information

Notes
12 refs.; Available from the INIS Liaison Officer for France, see the INIS website for current contact and E-mail addresses