Biological impact of low dose-rate simulated solar particle event radiation in vivo.
C57Bl6-lacZ animals were exposed to a range of low dose-rate simulated solar particle event (sSPE) radiation at the NASA-sponsored Research Laboratory (NSRL) at Brookhaven National Laboratory (BNL). Peripheral blood was harvested from animals from 1 to 12 days after total body irradiation (TBI) to quantify the level of circulating reticulocytes (RET) and micronucleated reticulocytes (MN-RET) as an early indicator of radiation-induced genotoxicity. Bone marrow lymphocytes and hippocampal tissues from each animal were collected at 12 days and up to two months, to evaluate dose-dependent late effects after sSPE exposure. Early hematopoietic changes show that the % RET was reduced up to 3 days in response to radiation exposure but recovered at 12 days postirradiation. The % MN-RET in peripheral blood was temporally regulated and dependant on the total accumulated dose. Total chromosome aberrations in lymphocytes increased linearly with dose within a week after radiation and remained significantly higher than the control values at 4 weeks after exposure. The level of aberrations in the irradiated animals returned to control levels by 8 weeks postirradiation. Measurements of chromosome 2 and 8 specific aberrations indicate that, consistent with conventional giemsa-staining methods, the level of aberrations is also not significantly higher than in control animals at 8 weeks postirradiation. The hippocampus was surveyed for differential transcriptional regulation of genes known to be associated with neurogenesis. Our results showed differential expression of neurotrophin and their associated receptor genes within 1 week after sSPE exposure. Progressive changes in the profile of expressed genes known to be involved in neurogenic signaling pathways were dependent on the sSPE dose. Our results to date suggest that radiation-induced changes in the hematopoietic system, i.e., chromosome aberrations in lymphocytes, are transient and do not persist past 4 weeks after radiation. On the other hand, alteration in the profile of genes known to be involved in neurotrophic functions in the hippocampal tissue appears to persist for up to 8 weeks after radiation exposure. Such temporal changes confirm that, although cytogenetic changes after a single dose of low-dose and low-dose-rate protons appear to be transient, the impact of this exposure is sufficient to lead to persistent dynamic changes in neuronal tissues long after the initial radiation exposure.
Chang
P Y
PY
SRI International, PN175, 333 Ravenswood Ave, Menlo Park, CA 94025, USA. pchang@sri.com
Doppalapudi
R
R
Bakke
J
J
Wang
A
A
Menda
S
S
Davis
Z
Z
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002869:Chromosome Aberrations / Q000528:radiation effects; D020869:Gene Expression Profiling; D042822:Genomic Instability / Q000528:radiation effects; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D008214:Lymphocytes / Q000378:metabolism / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009414:Nerve Growth Factors / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011829:Radiation Dosage; D017475:Receptors, Nerve Growth Factor / Q000235:genetics; D012156:Reticulocytes / Q000378:metabolism / Q000528:radiation effects; D016082:Solar System; D013026:Space Flight; D018561:Space Simulation; D013997:Time Factors
D009414:Nerve Growth Factors; D017475:Receptors, Nerve Growth Factor
PLoS One. 2009 Aug 03;4(8):e6486
19649251
Aviat Space Environ Med. 2003 Jul;74(7):746-52
12862329
Mutat Res. 1995 Jun;347(1):21-4
7596363
Cell Mol Life Sci. 2008 Jun;65(12):1842-53
18500641
J Neurosci. 2002 Jan 15;22(2):404-12
11784785
Environ Mol Mutagen. 1997;30(3):264-72
9366904
Acta Physiol (Oxf). 2010 Mar;198(3):277-85
19624551
Radiat Res. 2005 Oct;164(4 Pt 2):481-6
16187753
Neurodegener Dis. 2008;5(3-4):228-31
18322398
Glia. 2007 Feb;55(3):317-27
17115416
Mutat Res. 2000 Mar 3;466(1):87-96
10751730
J Neurosci. 2003 Oct 8;23(27):9116-22
14534245
Int J Radiat Biol. 1996 Oct;70(4):375-83
8862448
Neurobiol Learn Mem. 2009 Oct;92(3):429-38
19531380
Eur J Neurosci. 2008 Jun;27(11):2999-3008
18540883
Neurosci Lett. 2007 May 17;418(2):143-8
17400386
Radiat Res. 2008 Mar;169(3):280-7
18302490
Mutat Res. 1998 Aug 3;404(1-2):97-100
9729305
Mutat Res. 1993 Oct;292(2):137-43
7692250
Radiat Res. 2009 Jul;172(1):30-41
19580505
J Biol Chem. 2003 May 30;278(22):19956-65
12639970
Radiat Prot Dosimetry. 2003;104(3):199-210
14565726
Mutat Res. 1996 Sep 23;356(2):135-45
8841478
J Neurochem. 2005 Dec;95(5):1495-503
16219029
Radiat Res. 2000 Jan;153(1):110-21
10630984
Radiat Prot Dosimetry. 2009 Oct;136(4):297-303
19825832
Mutat Res. 1996 Dec 20;371(3-4):283-92
9008730
Int J Radiat Biol. 1996 Apr;69(4):437-46
8627126
Lancet Oncol. 2006 May;7(5):431-5
16648048