Gene Expression Profile of Human Lymphocytes Exposed to²¹¹At α Particles

Abstract

In this study, the Whole Human Genome 44K DNA microarray assay was used for the first time to obtain gene expression profiles in human peripheral blood lymphocytes 2 h after exposure (in suspension) to 6.78 MeV mean energy alpha particles from extracellular (211)At. Lymphocytes were exposed to fluences of 0.3-9.6 x 10(6) alpha particles/cm(2) [corresponding to mean absorbed alpha-particle doses (D(alpha)) of 0.05-1.60 Gy] over 30 min. Significantly modulated expression was identified in 338 early-response genes. Up-regulated expression was evident in 183 early-response genes, while the remaining 155 were down-regulated. Over half of the up-regulated genes and 40% of the down-regulated genes had a known biological process related primarily to cell growth and maintenance and cell communication. Genes associated with cell death were found only in the up-regulated genes and those with development only in the down-regulated genes. Eight selected early-response genes that displayed a sustained up- or down-regulation (CD36, HSPA2, MS4A6A, NFIL3, IL1F9, IRX5, RASL11B and SULT1B1) were further validated in alpha-particle-irradiated lymphocytes of two human individuals using the TaqMan(R) RT-qPCR technique. The results confirmed the observed microarray gene expression patterns. The expression modulation profiles of IL1F9, IRX5, RASL11B and SULT1B1 genes demonstrated similar trends in the two individuals studied. However, no significant linear correlation between increasing relative gene expression and the alpha-particle dose was evident. The results suggest the possibility that a panel of genes that react to alpha-particle radiation does exist and that they merit further study in a greater number of individuals to determine their possible value regarding alpha-particle biodosimetry.

Identification of gene-based responses in human blood cells exposed to alpha particle radiation

“…To date, Turtoi et al, [40] is the only other group to examine α-particle radiation induced genomic-wide transcriptional effects in isolated blood cells. This group employed a harvest time of 1hr post-irradiation using a dose range of 0.05 - 1.6 Gy of α-particle radiation.…”

Differential gene expression in human fibroblasts after alpha-particle emitter211At compared with60Co irradiation

“…Expression profi les of 211 At and 60 Co 257 high-and low-LET irradiation might refl ect quantitative eff ects on cell fate for certain genes. Th is is supported by Turtoi (2010) who identifi ed fi ve potential genes for biodosimetry of 211 At irradiated lymphocytes. Th e eff ect of 211 At and 60 Co radiation on DSB has been previously measured for the normal fi broblast cells used in this study (Claesson et al 2007).…”

“…The majority of studies on transcriptional response to ionizing radiation have used low-LET radiation qualities (X-and γ -rays, and β -particles), while there are still relatively few reports on transcriptional responses following high-LET radiation (neutrons, α -particles, and heavy ions). However, the use of high-LET radiation on different biological systems has resulted in the identification of a number of Expression profi les of 211 At and 60 Co 251 gene expression profiles (Sokolov et al 2006, Kurpinski et al 2009, Seidl et al 2010, Turtoi 2010. The present knowledge of cell and tissue responses to high-LET irradiation on the molecular level is therefore relatively scarce compared to that for low-LET irradiation.…”

Rescue of CD8+ T cell vaccine memory following sublethal γ irradiation

“…3A). Moreover, IL-36γ has also been identified in α-particle irradiated human lymphocytes [21] and perhaps could serve as a biomarker of radiation exposure. Puzzling is the upregulation of mir101c by day 1 rescue as this microRNA has been reported to inhibit DNA double strand break repair [22].…”