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Journal of Radiation Research and Applied
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Targeted and non-targeted effects of ionizing

radiation

Omar Desouky a,*, Nan Ding b, Guangming Zhou b

a
Radiation Physics Department, National Center for Radiation Research and Technology, Egyptian Atomic Energy
Authority, Nasr City, Cairo, Egypt
b
Department of Space Radiobiology, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China

article info abstract

Article history: For a long time it was generally accepted that effects of ionizing radiation such as cell
Received 26 February 2015 death, chromosomal aberrations, DNA damage, mutagenesis, and carcinogenesis result
Accepted 6 March 2015 from direct ionization of cell structures, particularly DNA, or from indirect damage through
Available online 19 March 2015 reactive oxygen species produced by radiolysis of water, and these biological effects were
attributed to irreparable or misrepaired DNA damage in cells directly hit by radiation. Using
Keywords: linear non-threshold model (LNT), possible risks from exposure to low dose ionizing ra-
Target theory diation (below 100 mSv) are estimated by extrapolating from data obtained after exposure
Bystander effect to higher doses of radiation. This model has been challenged by numerous observations, in
Adaptive response which cells that were not directly traversed by the ionizing radiation exhibited responses
Radiation protection similar to those of the directly irradiated cells. Therefore, it is nowadays accepted that the
Linear non-threshold detrimental effects of ionizing radiation are not restricted only in the irradiated cells, but
also to non-irradiated bystander or even distant cells manifesting various biological effects.
Copyright © 2015, The Egyptian Society of Radiation Sciences and Applications. Production
and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).

diagnostic imaging. Natural radiation and radioactivity in the

1. Introduction
All living organisms are daily exposed to radiation. In addition
to diagnostic and therapeutic medical exposures, we are
exposed chronically to background radiation from cosmic
rays, radioactive waste, radon decay, nuclear tests, and acci-
dents. The contribution to dose from naturally occurring ra-
dionuclides is much larger. In recent years, it has become
evident that inhalation of the short-lived decay products of
222
Rn is one of the more important sources of natural expo-
sure. The diagnostic applications of ionizing radiation (IR) in
medicine include the use of X-rays and radioisotopes in
environment, along with diagnostic medical exposure, make
up the very largest part of the accumulated annual dose to
human beings who are not occupationally exposed to ionizing
radiation from other sources during their daily work activity.
Despite the vast benefits derived from various medical
applications, radiation can be harmful and is well established
as a carcinogen to living organisms (Little, 2003). The adverse
effects of radiation are grouped into two categories: deter-
ministic effects and stocohahstic effects. Deterministic effects
are based on cell killing and characterized by a threshold dose.
Below the threshold dose there is no clinical effect. Stochastic
effects are associated with long-term, low-level (chronic)

* Corresponding author.
E-mail address: omardesouky@yahoo.com (O. Desouky).
Peer review under responsibility of The Egyptian Society of Radiation Sciences and Applications.
http://dx.doi.org/10.1016/j.jrras.2015.03.003
1687-8507/Copyright © 2015, The Egyptian Society of Radiation Sciences and Applications. Production and hosting by Elsevier B.V. This is an
open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
248 J o u r n a l o f R a d i a t i o n R e s e a r c h a n d A p p l i e d S c i e n c e s 8 ( 2 0 1 5 ) 2 4 7 e2 5 4
exposure to radiation. With exposures above the threshold
dose the severity of the injury increases with dose. The
probabilities of experiencing detrimental effects from expo-
sure to low-dose radiation are estimated by extrapolating
from data obtained after exposure to high-dose radiation,
using a linear model without a threshold (the LNT model).
Using this model, possible risks from exposure to low dose
ionizing radiation (below 100 mSv) are estimated by extrapo-
lating from data obtained after exposure to higher doses of
radiation (Matsumoto, Tomita, Otsuka &, Hatashita, 2009).
The LNT model has been widely used to establish interna-
tional rules and standards of radiation protection (ICRP). It
follows the notion that increases in the physical energy
deposition of IR linearly increases the carcinogenic risk with
increasing dose.
The conventional model, based on direct targeted effects of
radiation, has developed in radiobiology and it has been
extended to apply to radiation health risks and to guide radi-
ation protection practice. The radiation effects have been
explained using target theory. According to this, deleterious
effects of IR, such as mutation and carcinogenesis, are
attributed to damage to a cellular target, usually identified as
nuclear DNA via direct absorption of radiation energy, the
consequences of which are expressed in the surviving irradi-
ated cells (UNSCEAR 1993).
Although this model is applied carefully and conserva-
tively, there is room for concern about the validity of the low
dose exposure risks obtained in this way because a number of
findings have accumulated which cannot be explained by the
classical “target theory” of radiation biology. Specific cellular
responses observed in response to low dose and/or low dose-
rate radiation have been described as the radioadaptive
response, the radiation-induced bystander response, low-
dose hyper-radiosensitivity, and genomic instability. All of
these phenomena are considered to be responses to radiation
which involve non-targeted molecules or molecules which
have not interacted directly with radiation (Waldren 2004).
The propagation of damaging effects from irradiated to non-
irradiated bystander cells would, presumably, result in
supra-linear doseeresponse relationships. In contrast, the
expression of adaptive responses that mitigate the initial
damaging effects induced by radiation would suggest an infra-
linear doseeresponse relationship or the existence of a
threshold dose, below which there would be no risk.
2. Conventional interactions of ionizing
radiation with biological matter
2.1. Interaction types
Ionizing radiation is energetic and penetrating. Many of its
chemical effects in biological matter are due to the geometry
of the initial physical energy deposition events, referred to as
the track structure. Ionizing radiation exists in either partic-
ulate or electromagnetic types. The particulate radiation in-
teracts with the biological tissue either by ionization or
excitation. The ionizations and excitations that it produced
tend to be localized, along the tracks of individual charged
particles. Whereas the photon can penetrate matter without
interacting, it can be completely absorbed by depositing its
energy, or it can be scattered (deflected) from its original di-
rection and deposit part of its energy as follows:
1. Photoelectric interaction: a photon transfers all its energy
to an electron located in one of the atomic shells, usually
the outer shell. The electron is ejected from the atom and
begins to pass through surrounding matter.
2. Compton scattering: only a portion of the photon energy is
absorbed and a photon is scattered with reduced energy.
The photon that is produced leaves in a different direction
than that of the original photon with different energy.
3. Pair production: the photon interacts with the nucleus in
such a way that its energy is converted to matter producing
a pair of particles, an electron and a positively charged
positron. This only occurs with photons with energies in
excess of 1.02 MeV. (Hall & Giaccia, 2011)
3. Direct and indirect effect
Radiation damage to the cell can be caused by the direct or
indirect action of radiation on the DNA molecules. In the
direct action, the radiation hits the DNA molecule directly,
disrupting the molecular structure. Such structural change
leads to cell damage or even cell death. Damaged cells that
survive may later induce carcinogenesis or other abnormal-
ities. This process becomes predominant with high-LET radi-
ations such as a-particles and neutrons, and high radiation
doses. In the indirect action, the radiation hits the water
molecules, the major constituent of the cell, and other organic
molecules in the cell, whereby free radicals such as hydroxyl
(HO
) and alkoxy (RO2
) are produced.
Free radicals are characterized by an unpaired electron in
the structure, which is very reactive, and therefore reacts with
DNA molecules to cause a molecular structural damage.
Hydrogen peroxide, H2O2, is also toxic to the DNA molecule.
The result of indirect action of radiation on DNA molecules is
the impairment of function or death of the cell. The number of
free radicals produced by ionizing radiation depends on the
total dose. It has been found that the majority of radiation-
induced damage results from the indirect action mechanism
because water constitutes nearly 70% of the composition of
the cell (Saha, 2013).
In addition to the damages caused by water radiolysis
products (i.e. the indirect effect), cellular damage may also
involve reactive nitrogen species (RNS) and other species
(Wardman, 2009), and can occur also as a result of ionization
of atoms on constitutive key molecules (e.g. DNA). The ulti-
mate result, of direct and indirect effects, is the development
of biological and physiological alterations that may manifest
themselves seconds or decades later. Genetic and epigenetic
changes may be involved in the evolution of these alterations
(Koturbash, 2008).(Fig. 1)
X-ray and g-ray photons deposit energy in tissue in a highly
dispersed manner, characterized as low “linear energy trans-
fer” (LET). IR can be either low LET (sparsely ionizing) or high
LET (densely ionizing). Photons are low LET radiation, dis-
playing a very broad energy distribution in tissue, and the
peak dose is located relatively close to the surface. Heavy
 J o u r n a l o f R a d i a t i o n R e s e a r c h a n d A p p l i e d S c i e n c e s 8 ( 2 0 1 5 ) 2 4 7 e2 5 4
Fig. 1 e Direct and indirect actions of radiation (modified
from Hall & Giaccia, 2011).
charged particles are high LET and interact with matter by
depositing energy quite differently from photons. Because of
their large mass, compared with electrons, charged particles
travel in straight trajectories as they penetrate tissue
(Furusawa, 2014; Weber & Kraft, 2009).
4. Paradigm shift in target theory
The LNT theory assumes a linear relationship between DNA
damage in the form of double-strand breaks (DSB), that each
DSB will have the same probability of inducing a cell trans-
formation, and that each transformed cell will have the same
probability of developing into a cancer (Tubiana, Feinendegen,
Yang, & Kaminski, 2009). Thus, cancer is thought to result
from mutagenic DNA damage to a single cell caused by a
single radiation track (Little et al., 2009). A low LET dose of
1 mGy is delivered to one cell nucleus by one electron track
(NCRP, 2001). The LNT assumption is easy to implement uti-
lizing the equivalent dose (biological damage weighted mea-
sure) and the effective dose (equivalent dose multiplied by a
tissue weighting factor). Expected cancer cases are easily
calculated based on the summed effective dose (person-sie-
vert) for an irradiated population (Scott, 2008).
The LNT assumption does not consider the role of biolog-
ical defense mechanisms, but assumes that cancer risk pro-
ceeds in a proportionate linear fashion without a threshold to
a point of zero dose through the origin. The LNT assumption
with a low dose and dose rate effectiveness factor (DDREF)
guarantees that any radiation dose, no matter how small, in-
creases the risk of cancer.
The validity of using this doseeresponse model is contro-
versial because evidence accumulated over the past decade
has indicated that living organisms, including humans,
respond differently to low dose/low dose-rate radiation than
249
they do to high dose/high dose-rate radiation (Waldren, 2004).
These effects have been termed “non-(DNA)-targeted” (Ward,
1999) and include radiation-induced bystander effects (Iyer &
Lehnert, 2000), genomic instability (Wright, 1998, 2000),
adaptive response (Wolff, 1998), low dose hyper-
radiosensitivity (HRS) (Joiner, 2001), delayed reproductive
death and induction of genes by radiation (Amundson et al.,
2001). An essential feature of “non-targeted” effects is that
they do not require a direct nuclear exposure by irradiation to
be expressed and they are particularly significant at low doses.
5. Radiation induced bystander effects
The ionizing radiation-induced bystander effects (RIBE) is
broadly defined as the occurrence of biological effects in un-
irradiated cells as a result of exposure of other cells in the
population to radiation. Bystander effects have been mainly
observed in high density cell cultures exposed to low fluences
of a particles wherein only a small fraction of cells is irradiated
(Nagasawa & Little, 1992).
RIBE show non-linear doseeresponse; they are more pro-
nounced at low doses of radiation and tend to disappear,
though not always, at high radiation doses, suggesting an on-
off mechanism. As a result, they are frequently linked to low-
dose radiation effects and thus to radiation protection
(Morgan & Bair, 2013). Obviously, such non-targeted effects
change the actual radiation target size and give rise to non-
linear responses in cell populations and tissues. Moreover,
they put very much into question the overall validity of the
LNT hypothesis (Morgan & Sowa, 2007).
RIBE have been observed in a variety of endpoints
including DNA damage induction (Yang, Assad, & Held, 2005),
as well as in the induction of mutations, micronuclei (MN)
formation (Azzam, De Toledo, Spitz, & Little, 2002; Huo,
Nagasawa, & Little, 2001; Kashino et al., 2004; Zhou, 2000),
sister chromatid exchanges (SCE), chromosomal instability
(Limoli & Giedzinski, 2003; Lorimore et al., 1998), trans-
formation (Sawant, Randers-Pehrson, Geard, Brenner, & Hall,
2001), cell death or apoptosis (Belyakov, Folkard, Mothersill,
Prise, & Michael, 2002), altered gene expression (Iyer &
Lehnert, 2000), differentiation (Gerashchenko & Howell,
2003), and alteration in the microRNAs (miRNAs) profile
(Koturbash, Zemp, Kolb, & Kovalchuk, 2011; Kovalchuk et al.,
2010). All these manifestations of RIBE require DNA damage.
6. Probable mechanisms of the bystander
effects
Non-targeted effect represents a paradigm shift in our un-
derstanding of the mechanism (s) of how radiation might
exert its effects. It is likely that multiple pathways are
involved in signaling the response from an irradiated cell to a
non-irradiated cell, and that different cell types will respond
differently to the signaling pathways stimulated. It appears
that a bystander signal may be transmitted either by direct
cell-to-cell contact or through soluble factors released into the
culture medium (Little, 2006).
250 J o u r n a l o f R a d i a t i o n R e s e a r c h a n d A p p l i e d S c i e n c e s 8 ( 2 0 1 5 ) 2 4 7 e2 5 4
6.1. Cell-to-cell communications
The ability of cells to communicate with one another plays a
crucial role in the radiation induced bystander phenomenon.
Cell-to-cell communication is a complicated multistage pro-
cess. However published literature (Nikjoo & Khvostunov
(2004)) identified two main pathways of cell signaling
involved in the radiation induced bystander phenomenon
short range Gap Junctional Intercellular Communication
(GJIC) and long range Distant Cell Signaling Intercellular
Communication (DSIC), mediated by soluble transmissible
factors and propagated by Brownian active or passive diffu-
sive motion.
One of the reported mechanisms of the RIBE is the
gapejunction mediated intercellular communication (GJIC)
which depends on the intercellular gap junctions' ability to
transmit signals from irradiated to unirradiated cells (Azzam,
de Toledo, & Little, 2001). GJIC is mainly regulated by the
expression and phosphorylation of connexin43 protein (C x
43) which is located in gap junctions (Dowling-Warriner &
Trosko, 2000). Evidence for the involvement of GJIC in propa-
gation of bystander effects has been derived from studies with
a particle, b particle, g-rays, and HZE radiations. These studies
highlight the relevance of bystander responses to radio-
therapy, diagnostic radiology, and risk of environmental and
occupational exposures (Howell et al., 2006).
Participation of GJIC in stress-induced bystander effects is
not unique to ionizing radiation; it has also been described in
high density cell populations exposed to chemotherapeutic
agents. Toxicity of these compounds was enhanced by func-
tional gapejunction communication in target cells (Jensen &
Glazer, 2004).
6.2. ROS & RNS
Direct intercellular communication is not unique in propa-
gating radiation-induced non-targeted effects. A wealth of
data has also shown the critical importance of secreted
diffusible factors in the expression of radiation-induced non-
targeted effects (Mothersill & Seymour, 2004). TGF-b,
interleukin-8, serotonin and others have been implicated in
propagation of bystander effects (Lehnert & Goodwin, 1997).
The other proposed mechanisms of RIBE is known as a
medium-mediated bystander effect, and is based on the
ability of irradiated cells to excrete intracellularly-generated
low-molecular-weight factors in the growth medium (e.g.
ROS, cytokines, calcium ions, small RNAs) that are then
received by unirradiated cells (Merrifield & Kovalchuk, 2013).
There is wealth of evidence that ROS contribute to the
bystander effect extracellularly and also intracellularly
through a continuous cascade of events (Azzam et al., 2002).
ROS are produced directly by the irradiated cells as radiolytic
products or indirectly via inflammatory process and pass to
neighboring bystander cells through passive diffusion, gap
junctions, or active transport (Azzam, de Toledo, & Little,
2003). Although, most ROS have a short half-life and cause
damage locally, hydrogen peroxide (H2O2) has relatively
longer half-life. It can also migrate freely across plasma
membranes and travel long distances causing DNA damage at
distant sites (Sokolov, Dickey, Bonner, & Sedelnikova, 2007).
Furthermore, hydroxyl radicals and to a lesser extent the
singlet molecular oxygen can react with DNA, as well as with
proteins and lipids (Hussain, Hofseth, & Harris, 2003), result-
ing in the modulation of their functions.
With regard to radiation exposure, there are at least two
main factors which play an important role in radiation-
induced bystander signaling, the quality and the quantity of
the radiation. The involvement of the quality of radiation
exposure in RIBE signaling pathways has been questioned and
some experimental work (Lorimore, Coates, Scobie, Milne, &
Wright, 2001) suggested that the gap junction intercellular
communication is more likely to be induced by high LET ra-
diation (Should be careful about this point! are there follow-up
studies?). Whereas bystander signal propagation, mediated
via distant intercellular communication mechanisms, is more
likely to be triggered by low LET radiation. Thus, Mothersill
and Seymour (Mothersill & Seymour, 1998) demonstrated that
the cell to cell contact is not required to induce bystander
responses in non-targeted cells after low LET irradiation.
Overall, several studies challenge the traditional paradigm
that the important biological effects of ionizing radiation are
due to DNA damage induced as a result of direct interaction of
the radiation track with the cell nucleus. They indicate that
irradiated and non-irradiated cells interact, and oxidative
metabolism and intercellular communication have an essen-
tial role in signaling events leading to radiation-induced
bystander effects. However, clear evidence explaining how
these events occur is still lacking. Regardless, the occurrence
of bystander effects implies that the modeling of dose
response relationships based on the number of irradiated cells
may not be a valid approach (Little, 2003).
However, despite the enormous amount of data on RIBE,
until today, their nature remains elusive; some studies have
clearly shown that there is no evidence of any bystander effect
using various biological endpoints (Terzoudi, Donta-
Bakoyianni, Iliakis, & Pantelias, 2010).
The relatively unclear results regarding the mechanisms
underlying RIBE as well as the controversial results from
various experimental studies and systems indicate that the
research on bystander effects will serve as an interesting
scientific playground for debate in current and future radio-
biology. The experimental evidence on RIBE, indicate that a
more analytical and mechanistic in depth approach is needed
to secure an answer to one of the most interesting questions
in radiobiology (Vasiliki et al., 2015).
7. Radiation-induced adaptive response
(RIAR)
The “adaptive response” is a phenomenon generally induced
by low dose/low LET radiation that protects cells and whole
organisms against endogenous damage or damage due to a
subsequent dose of radiation (Wolff, 1992). Data generated
over the last three decades suggest that exposure of
mammalian cells, including human cells, to low doses of low
LET radiation (e.g. X-rays, g-rays, b particles) induces molec-
ular processes that are different from those induced by high
dose radiation (Feinendegen, Paratzke, & Neumann, 2007).
Such processes were found to be protective against stress
 J o u r n a l o f R a d i a t i o n R e s e a r c h a n d A p p l i e d S c i e n c e s 8 ( 2 0 1 5 ) 2 4 7 e2 5 4
measured by several biological endpoints (de Toledo & Azzam,
2006). Radiation-induced adaptive responses were dependent
on the adapting dose, dose rate, expression time, culture
conditions and stage of the cell cycle (Shadley, 1994). Chronic
exposure of mouse embryo fibroblasts to cobalt-60 g-radiation
at doses as low as 10 cGy protected the cells not only against
damage from endogenous metabolic processes, but also
against neoplastic transformation by a subsequent large acute
radiation exposure (Azzam, Raaphorst, & Mitchel, 1994).
Peripheral blood lymphocytes isolated from a group of 41
temporary nuclear plant workers receiving doses ranging
from 0 to 10 mSv showed no increase in the baseline micro-
nuclei frequencies as compared to the control values before
the in vivo dose (Thierens et al., 2002). After an in vitro chal-
lenging dose of 3.5 Gy 60Co g-rays, given either at a high-dose
rate (1 Gy/min) or a low-dose rate (4 mGy/min), the number of
micronuclei was statistically lower for the exposed persons as
compared to the non-exposed persons. Interestingly, the level
of adaptation was elevated if the challenging dose was given
at a low-dose rate.
A definitive proof of adaptive response belonging to the
group of non-targeted effects came from a study by Iyer and
Lehnert, demonstrating that non-irradiated human lung
fibroblast cells (HFL-1) were able to adapt if grown in a me-
dium transferred from HFL-1 cells, irradiated with either
0.1 Gy g-rays or 0.1 Gy a-particles (Iyer & Lehnert, 2002). The
adaptation was shown as increased clonogenic survival after a
challenging dose of 2 or 4 Gy g-rays, or 1.0 or 1.9 Gy a-particles,
respectively. Adaptive response was found to be associated
with a decreased level of p53 protein, increased level of
intracellular ROS as well as increased level of DNA repair
protein AP-endonuclease. The study suggested that non-
targeted cells are able to adapt after receiving an extracel-
lular signal.
There are three major cellular defense systems against
ionizing radiation that comprise the radioadaptive response
(Tubiana, Arengo, Averbeck, & Masse, 2007): (1) protection
against reactive oxygen species (ROS) by antioxidant mole-
cules (such as glutathione) and detoxifying enzymes (such as
catalase and superoxide dismutase); (2) DNA repair, particu-
larly for double-strand breaks, that disappears at doses
>0.5 Gy; and (3) elimination of genomically damaged cells by
immune defenses and apoptosis at doses as low as a few mSv.
The hormesis response is associated with increased lifespan,
and decreased mutations, chromosome aberrations,
neoplastic transformations, cancer, and congenital malfor-
mations (Kant, Chauhan, & Sharma, 2003).
The adaptive response occurs at dose values ranging from
0.01 to 0.5 Gy and at dose rate values ranging from 0.01 to
1.0 Gy/min (Aurengo, Averbeck, & Bonnin, 2005). The radio-
adaptive response appears most beneficial at doses <0.1 Gy.
The response begins to disappear at doses >0.2 Gy of low-LET
radiation and is rarely seen at a dose of >0.5 mGy. However,
the probability of apoptosis appears to increase in a linear
fashion beyond 0.5 mGy (Feinendegen et al., 2007).
The bottom line for most of the studies on the adaptive
response is that biological processes are activated by low
doses of ionizing radiation that trigger repair and protective
processes and decrease the risk for late effects of radiation.
These adaptive processes support the possibility that
251
intervention that enhances these normal processes is possible
and may provide an avenue to modify and decrease the risk
for cancer induced by low doses of ionizing radiation (Brooks,
2005).
8. Radiation protection
Radiological protection is a science-based discipline in which
concepts, methods, and procedures are developed to be used
for the protection of humans and the environment from the
harmful effects of ionizing radiation. More specifically,
radiological protection has the objective of reducing the like-
lihood of radiation-induced stochastic effects, in particular
cancer, and preventing deterministic effects, also called ‘tis-
sue reactions’.
Recommendations and practical guidance for radiological
protection have been developed by the International Com-
mission on Radiological Protection (ICRP) for more than 80
years and in its 2007 Recommendations the Commission has
described its latest system of protection with this aim in mind
(Menzel, & Harrison, 2012).
Almost all regulatory requirements authorizing activities
that use ionizing radiation such as in industry, health, agri-
culture, and basic research, is based on the radiation protec-
tion concept that hinges on the acceptance of the linear non-
threshold (LNT) theory.
LNT implies that any dose, no matter how low, can pose
risks for genetic (hereditary) defects or cause cancer. Cancer
risk is assumed to increase linearly with increasing radiation
dose, with no threshold. LNT was derived using statistically
significant doseeresponse (DR) relationship between radia-
tion dose received by the survivors of the atomic bomb ex-
plosions in Hiroshima and Nagasaki and the observed health
effects, mainly hereditary disorders and cancer (Decades
later, non-cancer risks are also derived from the same popu-
lation). The DR was based on the observable significant clin-
ical/deterministic effects that were seen on population
exposed at high doses, from 0.2 Gy upwards. Below this dose,
there were no observable effects seen on the population.
Nevertheless, DR is assumed to be linear down to zero dose.
The extrapolation to zero of the DR has not been supported by
sufficient evidence/data in man to show its linearity at low
doses. However, this assumption has been accepted to be the
conservative and most careful approach to address the
delayed effects of ionizing radiation, and to estimate health
risks at low doses (Aleta, 2009).
The LNT model is being challenged particularly in relation
to the environment because it is now clear that at low doses of
concern in radiation protection, cells, tissues and organisms
respond to radiation by inducing responses which are not
readily predictable by dose. These include adaptive responses,
bystander effects; genomic instability and low dose hyper-
sensitivity. The phenomena contribute to observed radiation
responses and appear to be influenced by genetic, epigenetic
and environmental factors, meaning that dose and response
are not simply related and the modeling of dose response re-
lationships based on the number of irradiated cells may not be
a valid approach (Little, 2003).
252 J o u r n a l o f R a d i a t i o n R e s e a r c h a n d A p p l i e d S c i e n c e s 8 ( 2 0 1 5 ) 2 4 7 e2 5 4
ICRP in its new review (2007), considered possible chal-
lenges to its linear non-threshold model but concluded that
for the purposes of radiological protection, it is scientifically
reasonable to assume that the incidence of cancer or heredi-
tary disorders will rise in direct proportion to an increase in the
equivalent dose in the relevant organs and tissues, below
about 100 mSv. ICRP also considered issues such as cellular
adaptive responses, genomic instability and bystander
signaling but notes that ‘since the estimation of nominal
cancer risk coefficients is based upon direct human epidemi-
ological data, any contribution from these biological mecha-
nisms would be included in that estimate’ (Wrixon, 2008).
BEIR VII concluded that the available biological and bio-
physical low dose data support a linear-no-threshold (LNT)
risk model. According to this model, even the smallest dose of
radiation has the potential to cause a small increase in health
risk to humans. The reports from UNSCEAR and the ICRP
concluded that the LNT hypothesis remains a prudent basis
for radiation protection at low doses and low dose rates, but
may not reflect biological differences and risks in the low dose
region (Morgan & Bair, 2013)
9. Conclusion
This paper has reviewed new information that demonstrates
that bystander effects and adaptive responses which impor-
tant parts of the response of molecules, cells and tissues to
ionizing radiation. It is important to recognize that these new
observations make it possible to shift from the assumption
that radiation has to interact with a cell directly only.
Acknowledgments
This work was supported by TWAS-UNISCO, Chinese acad-
emy of science and institute of modern physics.
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