PMID- 24370566
OWN - NLM
STAT- MEDLINE
DCOM- 20150309
LR  - 20220317
IS  - 1872-7980 (Electronic)
IS  - 0304-3835 (Linking)
VI  - 356
IP  - 1
DP  - 2015 Jan 1
TI  - Bystander effects as manifestation of intercellular communication of DNA damage 
      and of the cellular oxidative status.
PG  - 58-71
LID - S0304-3835(13)00855-0 [pii]
LID - 10.1016/j.canlet.2013.12.017 [doi]
AB  - It is becoming increasingly clear that cells exposed to ionizing radiation (IR) 
      and other genotoxic agents (targeted cells) can communicate their DNA damage 
      response (DDR) status to cells that have not been directly irradiated (bystander 
      cells). The term radiation-induced bystander effects (RIBE) describes facets of 
      this phenomenon, but its molecular underpinnings are incompletely characterized. 
      Consequences of DDR in bystander cells have been extensively studied and include 
      transformation and mutation induction; micronuclei, chromosome aberration and 
      sister chromatid exchange formation; as well as modulations in gene expression, 
      proliferation and differentiation patterns. A fundamental question arising from 
      such observations is why targeted cells induce DNA damage in non-targeted, 
      bystander cells threatening thus their genomic stability and risking the 
      induction of cancer. Here, we review and synthesize available literature to 
      gather support for a model according to which targeted cells modulate as part of 
      DDR their redox status and use it as a source to generate signals for neighboring 
      cells. Such signals can be either small molecules transported to adjacent 
      non-targeted cells via gap-junction intercellular communication (GJIC), or 
      secreted factors that can reach remote, non-targeted cells by diffusion or 
      through the circulation. We review evidence that such signals can induce in the 
      recipient cell modulations of redox status similar to those seen in the 
      originating targeted cell - occasionally though self-amplifying feedback loops. 
      The resulting increase of oxidative stress in bystander cells induces, often in 
      conjunction with DNA replication, the observed DDR-like responses that are at 
      times strong enough to cause apoptosis. We reason that RIBE reflect the function 
      of intercellular communication mechanisms designed to spread within tissues, or 
      the entire organism, information about DNA damage inflicted to individual, 
      constituent cells. Such responses are thought to protect the organism by 
      enhancing repair in a community of cells and by eliminating severely damaged 
      cells.
CI  - Copyright (c) 2013 Elsevier Ireland Ltd. All rights reserved.
FAU - Klammer, Holger
AU  - Klammer H
AD  - Institute of Medical Radiation Biology, University of Duisburg-Essen Medical 
      School, Essen, Germany.
FAU - Mladenov, Emil
AU  - Mladenov E
AD  - Institute of Medical Radiation Biology, University of Duisburg-Essen Medical 
      School, Essen, Germany.
FAU - Li, Fanghua
AU  - Li F
AD  - Institute of Medical Radiation Biology, University of Duisburg-Essen Medical 
      School, Essen, Germany.
FAU - Iliakis, George
AU  - Iliakis G
AD  - Institute of Medical Radiation Biology, University of Duisburg-Essen Medical 
      School, Essen, Germany. Electronic address: Georg.Iliakis@uk-essen.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20131224
PL  - Ireland
TA  - Cancer Lett
JT  - Cancer letters
JID - 7600053
RN  - 0 (Cytokines)
RN  - 0 (Reactive Nitrogen Species)
RN  - 0 (Reactive Oxygen Species)
SB  - IM
MH  - Apoptosis/radiation effects
MH  - Bystander Effect/*radiation effects
MH  - Cell Communication/*genetics
MH  - Cell Transformation, Neoplastic/radiation effects
MH  - Cytokines/biosynthesis/metabolism
MH  - DNA Damage/*radiation effects
MH  - DNA Repair/genetics
MH  - Gap Junctions
MH  - Genomic Instability/radiation effects
MH  - Humans
MH  - Oxidative Stress/*radiation effects
MH  - Reactive Nitrogen Species/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction/radiation effects
OTO - NOTNLM
OT  - Bystander effects
OT  - DNA damage signaling
OT  - Ionizing radiation
EDAT- 2013/12/29 06:00
MHDA- 2015/03/10 06:00
CRDT- 2013/12/28 06:00
PHST- 2013/10/11 00:00 [received]
PHST- 2013/12/13 00:00 [revised]
PHST- 2013/12/14 00:00 [accepted]
PHST- 2013/12/28 06:00 [entrez]
PHST- 2013/12/29 06:00 [pubmed]
PHST- 2015/03/10 06:00 [medline]
AID - S0304-3835(13)00855-0 [pii]
AID - 10.1016/j.canlet.2013.12.017 [doi]
PST - ppublish
SO  - Cancer Lett. 2015 Jan 1;356(1):58-71. doi: 10.1016/j.canlet.2013.12.017. Epub 
      2013 Dec 24.