PMID- 28441437
OWN - NLM
STAT- MEDLINE
DCOM- 20170906
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 4
DP  - 2017
TI  - Quantitative modeling of responses to chronic ionizing radiation exposure using 
      targeted and non-targeted effects.
PG  - e0176476
LID - 10.1371/journal.pone.0176476 [doi]
LID - e0176476
AB  - The biological effects of chronic ionizing radiation exposure can be difficult to 
      study, but important to understand in order to protect the health of 
      occupationally-exposed persons and victims of radiological accidents or malicious 
      events. They include targeted effects (TE) caused by ionizations within/close to 
      nuclear DNA, and non-targeted effects (NTE) caused by damage to other cell 
      structures and/or activation of stress-signaling pathways in distant cells. Data 
      on radiation damage in animal populations exposed over multiple generations to 
      wide ranges of dose rates after the Chernobyl nuclear-power-plant accident are 
      very useful for enhancing our understanding of these processes. We used a 
      mechanistically-motivated mathematical model which includes TE and NTE to analyze 
      a large published data set on chromosomal aberrations in pond snail (Lymnaea 
      stagnalis) embryos collected over 16 years from water bodies contaminated by 
      Chernobyl fallout, and from control locations. The fraction of embryo cells with 
      aberrations increased dramatically (>10-fold) and non-linearly over a dose rate 
      range of 0.03-420 muGy/h (0.00026-3.7 Gy/year). NTE were very important for 
      describing the non-linearity of this radiation response: the TE-only model 
      (without NTE) performed dramatically worse than the TE+NTE model. NTE were 
      predicted to reach (1/2) of maximal intensity at 2.5 muGy/h (0.022 Gy/year) and to 
      contribute >90% to the radiation response slope at dose rates <11 muGy/h (0.1 
      Gy/year). Internally-incorporated 90Sr was possibly more effective per unit dose 
      than other radionuclides. The radiation response shape for chromosomal 
      aberrations in snail embryos was consistent with data for a different endpoint: 
      the fraction of young amoebocytes in adult snail haemolymph. Therefore, radiation 
      may affect different snail life stages by similar mechanisms. The importance of 
      NTE in our model-based analysis suggests that the search for modulators of 
      NTE-related signaling pathways could be a promising strategy for mitigating the 
      deleterious effects of chronic irradiation.
FAU - Shuryak, Igor
AU  - Shuryak I
AD  - Center for Radiological Research, Columbia University, New York, NY, United 
      States of America.
LA  - eng
PT  - Journal Article
DEP - 20170425
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
SB  - IM
MH  - Animals
MH  - *Chernobyl Nuclear Accident
MH  - Chromosome Aberrations/*radiation effects
MH  - Environmental Exposure/*adverse effects
MH  - Lymnaea/*radiation effects
MH  - Models, Theoretical
MH  - Radiation Dosage
MH  - *Radiation, Ionizing
PMC - PMC5404850
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2017/04/26 06:00
MHDA- 2017/09/07 06:00
PMCR- 2017/04/25
CRDT- 2017/04/26 06:00
PHST- 2016/11/01 00:00 [received]
PHST- 2017/04/11 00:00 [accepted]
PHST- 2017/04/26 06:00 [entrez]
PHST- 2017/04/26 06:00 [pubmed]
PHST- 2017/09/07 06:00 [medline]
PHST- 2017/04/25 00:00 [pmc-release]
AID - PONE-D-16-43510 [pii]
AID - 10.1371/journal.pone.0176476 [doi]
PST - epublish
SO  - PLoS One. 2017 Apr 25;12(4):e0176476. doi: 10.1371/journal.pone.0176476. 
      eCollection 2017.