Identification of potential mRNA biomarkers in peripheral blood lymphocytes for human exposure to ionizing radiation.
Since early in the Atomic Age, biological indicators of radiation exposure have been sought, but currently available methods are not entirely satisfactory. Using cDNA microarray hybridization to discover new potential biomarkers, we have identified genes expressed at increased levels in human peripheral blood lymphocytes after ex vivo irradiation. We recently used this technique to identify a large set of ionizing radiation-responsive genes in a human cell line (Oncogene 18, 3666-3672, 1999). The present set of radiation markers in peripheral blood lymphocytes was identified 24 h after treatment, and while the magnitude of mRNA induction generally decreased over time, many markers were still significantly elevated up to 72 h after irradiation. In all donors, the most highly responsive gene identified was DDB2, which codes for the p48 subunit of XPE, a protein known to play a crucial role in repair of ultraviolet (UV) radiation damage in DNA. Induction of DDB2, CDKN1A (also known at C1P1/WAF1) and XPC showed a linear dose-response relationship between 0.2 and 2 Gy at 24 and 48 h after irradiation, with less linearity at earlier or later times. These results suggest that relative levels of gene expressions in peripheral blood cells may provide estimated of environmental radiation exposures.
Amundson
S A
SA
National Institutes of Health, National Cancer Institute, Bethesda, MD 20892, USA.
Do
K T
KT
Shahab
S
S
Bittner
M
M
Meltzer
P
P
Trent
J
J
Fornace
A J
AJ
D000328:Adult; D015415:Biomarkers; D002478:Cells, Cultured / Q000528:radiation effects; D056746:Cyclin G; D056766:Cyclin G1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000528:radiation effects*; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics; D008214:Lymphocytes / Q000528:radiation effects*; D020411:Oligonucleotide Array Sequence Analysis; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis*
D015415:Biomarkers; C534702:CCNG1 protein, human; C493956:CDKN1A protein, human; D056746:Cyclin G; D056766:Cyclin G1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; C117669:DDB2 protein, human; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D007378:Interleukins; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; C086984:XPC protein, human