当前位置： SCI文献检索 > RADIATION RESEARCH期刊下所有文献 > Developing Human Radiation Biodosimetry Models: Testing Cross-Species Conversion Approaches Using an Ex Vivo Model System.

Developing Human Radiation Biodosimetry Models: Testing Cross-Species Conversion Approaches Using an Ex Vivo Model System.

Abstract：

:In the event of a large-scale radiation exposure, accurate and quick assessment of radiation dose received would be critical for triage and medical treatment of large numbers of potentially exposed individuals. Current methods of biodosimetry, such as the dicentric chromosome assay, are time consuming and require sophisticated equipment and highly trained personnel. Therefore, scalable biodosimetry approaches, including gene expression profiles in peripheral blood cells, are being investigated. Due to the limited availability of appropriate human samples, biodosimetry development has relied heavily on mouse models, which are not directly applicable to human response. Therefore, to explore the feasibility of using non-human primate (NHP) models to build and test a biodosimetry algorithm for use in humans, we irradiated ex vivo peripheral blood samples from both humans and rhesus macaques with doses of 0, 2, 5, 6 and 7 Gy, and compared the gene expression profiles 24 h later using Agilent human microarrays. Among the dose-responsive genes in human and using non-human primate, 52 genes showed highly correlated expression patterns between the species, and were enriched in p53/DNA damage response, apoptosis and cell cycle-related genes. When these interspecies-correlated genes were used to build biodosimetry models with using NHP data, the mean prediction accuracy on non-human primate samples was about 90% within 1 Gy of delivered dose in leave-one-out cross-validation. However, tests on human samples suggested that human gene expression values may need to be adjusted prior to application of the NHP model. A "multi-gene" approach utilizing all gene values for cross-species conversion and applying the converted values on the NHP biodosimetry models, gave a leave-one-out cross-validation prediction accuracy for human samples highly comparable (up to 94%) to that for non-human primates. Overall, this study demonstrates that a robust NHP biodosimetry model can be built using interspecies-correlated genes, and that, by using multiple regression-based cross-species conversion of expression values, absorbed dose in human samples can be accurately predicted by the NHP model.

journal_name

Radiat Res

journal_title

Radiation research

authors

Park JG,Paul S,Briones N,Zeng J,Gillis K,Wallstrom G,LaBaer J,Amundson SA

doi

10.1667/RR14655.1

subject

Has Abstract

pub_date

2017-06-01 00:00:00

pages

708-721

issue

eissn

0033-7587

issn

1938-5404

journal_volume

187

pub_type

杂志文章

在线工具

Developing Human Radiation Biodosimetry Models: Testing Cross-Species Conversion Approaches Using an Ex Vivo Model System.