W Hoffmann1, I Schmitz-Feuerhake. 1. Environmental Research and Technology Centre, University of Bremen (UFT), Germany. hoffmann@bips.uni.bremen.de
Abstract
QUESTION: Quantitative cytogenetic analysis of structural chromosome aberrations in human peripheral blood lymphocytes is widely used as an assay to detect and quantify exposure to a variety of clastogens. Unstable chromosome rearrangements, dicentric chromosomes (dic) and centric ring chromosomes (centric r), are routinely used as biomarkers to assess human exposure to ionizing radiation ("biological dosimetry"). In the moderate- to high-dose range many authors consider the dic assay sufficiently radiation-specific for both practical and legal purposes. However, specificity has never been evaluated in quantitative terms. The high sensitivity of the assay would in principle allow for applications in the range of low-dose exposure which has been a major concern in epidemiologic studies. Validity of the assay then critically depends on specificity. METHODS: A mathematical model is proposed which includes as parameters the decline of dicentric aberrations in vivo, the linear dose coefficient for the induction of dic and the average total radiation exposure of the population. To assess radiation-specificity of the dic assay the equilibrium dicentric rate due to radiation is compared to measurements of the background rate of dic in unexposed controls. RESULTS: Environmental and medical radiation combined account for at least about 80% of the average background level of dicentrics. CONCLUSION: It is concluded that the dicentric assay is highly specific for ionizing radiation and can therefore be used to assess prior exposure in the dose range of interest in environmental epidemiology.
QUESTION: Quantitative cytogenetic analysis of structural chromosome aberrations in human peripheral blood lymphocytes is widely used as an assay to detect and quantify exposure to a variety of clastogens. Unstable chromosome rearrangements, dicentric chromosomes (dic) and centric ring chromosomes (centric r), are routinely used as biomarkers to assess human exposure to ionizing radiation ("biological dosimetry"). In the moderate- to high-dose range many authors consider the dic assay sufficiently radiation-specific for both practical and legal purposes. However, specificity has never been evaluated in quantitative terms. The high sensitivity of the assay would in principle allow for applications in the range of low-dose exposure which has been a major concern in epidemiologic studies. Validity of the assay then critically depends on specificity. METHODS: A mathematical model is proposed which includes as parameters the decline of dicentric aberrations in vivo, the linear dose coefficient for the induction of dic and the average total radiation exposure of the population. To assess radiation-specificity of the dic assay the equilibrium dicentric rate due to radiation is compared to measurements of the background rate of dic in unexposed controls. RESULTS: Environmental and medical radiation combined account for at least about 80% of the average background level of dicentrics. CONCLUSION: It is concluded that the dicentric assay is highly specific for ionizing radiation and can therefore be used to assess prior exposure in the dose range of interest in environmental epidemiology.
Authors: Soumen K Manna; Kristopher W Krausz; Jessica A Bonzo; Jeffrey R Idle; Frank J Gonzalez Journal: J Proteome Res Date: 2013-04-24 Impact factor: 4.466