BIOLOGICAL RESEARCH ON LOW DOSES
Anna Giovanetti ENEA UTBIORAD CR Casaccia Rome, Italy Operational Issues in Radioactive Waste Management and Nuclear Decomissioning An International Summer School 6th edition 8-12 September 2014, ISPRA JRC (Varese, Italy)
“Low dose” is defined as any dose between ambient levels of
radiation and the threshold that marks the boundary between
biopositive and bionegative effects (Luckey, 1999).
DEFINITION OF LOW DOSES
RADIATIONS’ EXPOSURE SOURCES IN US: CHANGES
Radon 37% Internal 5% Cosmic rays 5% Terrestrial 3% total natural 50% Nuclear medicine 12% Medical X rays 24% Fluoroscopy 12% Consumer product 2% Industrial
The evaluations of health effects of exposure to IR at low doses
and dose rates, is limited by the low statistical power of
epidemiological analyses (UNSCEAR: Biological Mechanisms Of
Radiation Actions At Low Doses, 2012) .
For interpolating the dose–response between data from
epidemiological investigations and incremental doses above
background exposures
it is needed to know the mechanisms of radiation
action and of response to irradiation
RISK FROM LOW DOSES
• Why is it so difficult to determine if low doses of radiation cause cancer?
• Background radiation is often higher than the level of added radiation exposure.
• There is a high and variable rate of cancer in the human population.
• There is no way to distinguish a radiation-induced cancer from a spontaneous cancer.
CANCER RISK FROM LOW DOSES
SINGLE HIT THEORY
• The long accepted radiobiological paradigm establishes that genetic damage is generated by direct interaction of radiation with DNA.
• Genetic damage or cell death are supposed to be caused by un-repaired or mis-repaired DNA lesions.
• THE INDIVIDUAL CELL IS THE UNIT OF RISK, thus the degree of damage is strictly related to the number of irradiated cells.
LNT HYPOTHESIS
The LNT hypothesis states that:
• Any amount of radiation may pose an increased risk for causing cancer hereditary effects
• Risk is directly proportional to dose and without a threshold.
• Other variables are insignificant comparing to dose.
LIMITS OF LNT
• The LNT theory does not predict any qualitative differences in
effects between low doses delivered at low dose-rates and high doses delivered at high dose-rates
• The LNT theory does not account for non-linear modifiers of risk such as:
• individual radio-sensitivity (age, immune-system, DNA repair enzymes…)
• synergistic or antagonistic effects with other exposures
In establishing risk for low dose exposures, two health endpoints
currently considered important:
cancer and heritable effects
More recently concerns have been raised regarding the low doses
induction of non-cancer diseases, particularly:
circulatory disease, cataract, immune system effects
LOW DOSES EFFECTS
ADVANCES IN RADIATION PROTECTION
X-ray apparatus used for treatment of epithelioma of the face, 1915. The tube is in a localizing shield; and a perforated sheet of metal is securely fashioned to the surface by adhesive plaste
Radiotherapy treatment machines
NON-TARGETED EFFECTS
As early as 1915, 20 years after Roentgen discovered X-rays, a report was published suggesting that ionizing radiation to one part of the body could result in effects in a distant part.
Further discoveries were published over the years but largely ignored as the field of radiobiology became dominated by target theory and the DNA paradigm.
Responses of cells and tissues to irradiation not fitting the standard DNA damage driven LNT model, have been considered non-targeted effects.
THE EFFECT OF ROENTGEN RAYS ON THE RATE OF GROWTH OF SPONTANEOUS TUMORS IN MICE
We have further noted that by one small dose of x-ray we could obtain in a certain proportion of animals a stimulation of the
lymphoid elements, preceded by a comparatively short period in
which the lymphocytes were below normal. This suggested an
explanation of certain therapeutic effects of x-ray.
We have avoided in this communication any discussion of the massive and contradictory literature on direct x-ray effects. We
are unaware of any experiments that bring out the above points.
Murphy and Norton, J Exp Med. Dec 1, 1915; 22(6): 800–803.
CHALLENGING OF THE TARGET THEORY Over a 10-year period from 1986 to 1996, the target theory was
challenged by four key lines of evidence
1. In 1986 de novo appearance of lethal mutations was observed in cells which had “recovered” from irradiation and successfully divided for several generations (Seymour et al., 1986).
2. Delayed appearance of de novo chromosome aberrations was demonstrated in bone marrow stem cell lineages derived from irradiated stem cells (Kadhim et al., 1992).
3. A very low dose exposure to alpha radiation resulted in more cells showing chromosome damage than could have been hit by the ionizing particles (Nagasawa and Little, 1992)
4. Medium from irradiated cells was found to cause similar levels of clonogenic cell death and genomic instability as direct irradiation (Mothersill and Seymour, 1997; Seymour and Mothersill, 1997).
NEW PARADIGM IN LOW DOSE RADIOBIOLOGY
Taken together, these papers started the scientific revolution establishing a new paradigm in low dose radiobiology which now
is accepted by most radiation biologists but still not fully
understood (from Mothersill and Seymour 2012)
REVIEW OF EPIDEMIOLOGIC STUDIES Chronic and acute exposures to low-doses have been supposed to be much more
mutagenic and carcinogenic than previously thought (Prasad et al. 2004), Basing on several epidemiology studies Little (2010) stated that non-targeted effects may challenge the LNT model, by increasing the effective target size.
In all these studies non-linear models may result strongly superior to the linear ones in fitting the data.
A recent analysis demonstrated in the 0-20 mSv colon dose sub-cohort of the 1950-90 A-bomb survivors, a positive correlation of exposure with all-solid cancer mortality several orders of magnitude above the slope at high doses (Dropkin 2007).
On contrary Cohen, analysing the same data has commented that for doses of less than 250 mSv the data are not inconsistent with a zero slope, or even with a negative slope (hormesis)
WHY NON-TARGETED EFFECTS ARE ASSOCIATED TO LOW DOSES?
• Non-targeted effects saturate with increasing dose, thus its role on radiation health effects is higher in the low doses range
• It has been suggested that the biological pathways involved in direct and indirect effects are different.
• in fact
• indirect effects were hypothesized to consist in an accelerated rate of naturally occurring genetic damage such as point
mutations,
• while the characteristic damage in the directly irradiated cells are breaks and deletions
HIGH AND LOW LET RADIATIONS
• High LET radiation induces a clustered DNA damage site (a) which is defined as multiple lesions within a few nm in a DNA molecule.
• This densely localized damage might distort the tertiary structure of DNA and consequently interfere with the binding of repair enzymes to the damage site.
• Low LET radiation creates randomly isolated damage (b).
NON-TARGETED EFFECTS
• GENOMIC INSTABILITY
• BYSTANDER EFFECT
• ADAPTIVE RESPONSE
• ABSCOPAL EFFECTS
• RELEASE OF CLASTOGENIC FACTORS
ANY OF THESE MAY MODIFY LNT ASSUMPTIONS FOR LOW DOSES
GENOMIC INSTABILITY
• Radiation-induced GI defines several potentially detrimental effects observed in the progeny of an irradiated cell, up to 30
cell divisions after irradiation:
• chromosomal rearrangements, micronuclei, transformation, gene amplifications, gene mutations and reduced plating
efficiency in cells derived from an irradiated cell
• In vivo GI has been related with the presence of inflammatory status and plasma clastogenic factors.
• The persistence of GI potentially leads to neoplastic transformation.
GENOMIC INSTABILITY: NON CLONAL TRANSMISSION
a) Following the single hit theory energy is deposited in the nucleus of the irradiated
cell, the damage is 'fixed' and transmitted
clonally to the progeny of that cell.
b) Radiation-induced genomic instability: different types of delayed effects occur
in the progeny of the irradiated cell, for
example, mutation (black), chromosomal
rearrangements (hatched), cell death
(cross) and/or aneuploidy (double-sized
cell)
MECHANISMS UNDERLYING GI
The current hypothesis to explain radiation-induced genomic instability is that
radiation can initiate a process in a cell that can be communicated to other cells and cause a cascade of cellular events that results in the destabilized genome
This can be perpetuated over time by a number of processes involving:
• reactive oxygen species
• cell-to-cell gap junction communication
• dead and dying cells in the unstable population
• secreted factors from unstable cells .
Giovanetti A, Deshpande T, Basso E. Persistence of genetic damage in mice exposed to low dose of X rays. Int J Radiat Biol. 2008, 84(3):227-35.
• 1 Gy mice showed 30 min, 24 h and 7 d after exposure, a significant increase DNA breaks compared to controls and 0,1 Gy mice, then damage decreased reaching controls’ values from 1 m.
• In contrast 0.1 Gy mice damage was initially not significantly different from controls but progressively increased and at 3 and 6 m from whole-body exposure, the percentage of DNA breaks was significantly higher compared to controls and to 1 Gy-irradiated mice.
DNA breaks in control mice
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MECHANISMS UNDERLYING GI
A study of gene expression changes associated
with radiation-induced GI did not identify a single
pathway dysregulated in unstable clones
suggesting multiple pathways might be
involved.
Particularly important is the hit cells' ability to
respond to the initial radiation insult, as studies
suggest that
the DNA repair genes XRCC2 and XRCC3 and the
catalytic subunit of DNA PK may play important
roles in maintaining chromosome stability
after cellular exposure to ionizing radiation.
GENOMIC INSTABILITY AND CANCER
• The loss of stability of the genome is now widely accepted as one of the most important aspects of cancer.
• The chromosome breakage syndromes, ataxia–telangiectasia, Nijmegen breakage syndrome, ataxia–
telangiectasia-like disorder, Bloom syndrome, Werner
syndrome and Fanconi anemia are human autosomal
recessive diseases characterized by inherited chromosomal
instability and cancer predisposition.
DNA MICROARRAY
• The development of DNA microarray technology in mid 1990s allowed for the first time to simultaneously check changes in the
expression of thousands of genes
• A DNA microarray is a collection of synthetic DNA probes attached to designated location, or spot, on a solid surface.
• The resulting "grid" of probes can hybridize to complementary "target" sequences derived from experimental samples to determine
the expression level of specific mRNAs in a sample (Y Grigoryev 2011)
DNA MICROARRAY
• The mRNA is extracted from cells and converted into cDNA, linked to a fluorescent appears on the chip with the corresponding DNA,
• emitting red fluorescence if a gene is expressed only in the tissue sample, green if a gene is expressed only in the irradiated tissue and different shades of yellow (red + green) if a gene is expressed in both tissues.
ALTERATIONS IN GENE EXPRESSION AND RADIATION-INDUCED GI
The expression profiles of irradiated chromosomally stable GM10115 clones with irradiated, unstable GM10115 clones were compared using the Genomic Solutions 1152 element human cancer cDNA chip
61 genes were identified as significant different and all were downregulated in the unstable clones
One of the genes identified was BRCA2 which showed an average 2.65-fold reduction in unstable clones.
BRCA2 protein functions as tumor suppressors and has multiple, complex roles in DNA damage-response pathway.
Differential expression of BRCA2 was an attractive candidate for a role in radiation-induced instability.
HUMAN SKIN MODEL SHOWS SIGNALING PATHWAY EFFECTS FROM LOW DOSE EXPOSURE
• In studies on a human skin tissue model, researchers at Pacific Northwest National
Laboratory used a systems biology approach to show that an ionizing radiation dose mimicking that received during a CT scan (5-100 cGy) is sufficient to alter genes in two (proliferating) cell layers: epidermis, the outer skin layer, and the dermis is beneath it.
• The researchers found 1452 genes altered in the dermis and 428 genes altered in the epidermis.
a) Green for Edu (analog of thymidine,incorporated into DNA during synthesis and repair) blue: DNA.
b) % of EdU-positive nuclei
per tissue section for epidermal keratinocytes and dermal fibroblasts 24 and 72 hrs post exposure to 3, 10, 50 and 200 cGy.
GENOMIC INSTABILITY: ROLE OF TELOMERES
Telomeres are highly specialized nucleoprotein structures that stabilize and protect the ends of chromosomes.
Telomeres play an essential role in preserving the integrity of genomes.
The telomere length of somatic cells shortens with age and with other endogenous and exogenous pathogenic factors.
When telomere dysfunction does
occur, the consequences can be
severe, including cellular senescence
and the formation of chromosomal
rearrangements likely to be
associated with carcinogenesis.
TELOMERES AND RADIATION
The relationship between the functionality of telomeres and radiation is complex: • Ionizing radiation can induce a shortening of
telomeres
• Telomeres’ dysfunction impairs DNA repair and enhances sensitivity to ionizing radiation.
LOW DOSE-TELOMERES-AGING
Over the last decade significant amounts of information about age-associated changes in astronaut health have been accumulating (decreases in bone mineralization and in muscle mass, cardiovascular changes, decreases in immune function early appearance of cataracts, changes in thyroid function, and loss of neural cells). The major theories of aging include protein cross linking, DNA damage, free radical damage, mitochondrial DNA damage and cellular senescence. Telomeres progressively shorten with age in most human tissues. There is mounting evidence that radiation, similar to what is present in space, may result in preferential telomere damage and this may explain some of the age-associated changes that we are observing in astronauts.
BYSTANDER EFFECT • Following irradiation with alpha particles of 1% of cells, 30%
presented an increasing of genetic damage (SCE).
• Thus irradiated cells communicated with non-irradiated cells via secreted factors and/or cell-to-cell gap junction, eliciting
responses in those cells that were not 'hit' by radiation.
Nagasawa and Little 1992
INDUCTION OF BE IN HACAT CELLS
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IN VIVO BYSTANDER EFFECT Evidence for bystander-induced double-strand breaks is now available for full-thickness human skin and airway-epithelium tissue models. Evidence for long-distance bystander communication in vivo comes from mouse shielded irradiation studies of DNA damage and DNA methylation in skin and spleen or the mouse haemopoietic system,
Perhaps the most extreme form of bystander communication reported involves communication between fish by water-borne signals
MECHANISMS UNDERLYING BE
A range of potential mediators of bystander signals have been
identified including nitric oxide, the cytokine TGFβ, other
inflammatory response markers and extra cellular DNA.
Calcium signalling may be implicated in the transduction of
bystander signals from the external medium into responding
cells
In summary there is now better evidence for bystander
signalling in vivo and this could conceivably modulate cancer
risk.
INDUCTION OF BE It is also important to note that a number of other agents have been reported to induce bystander-type responses. These include UV, heat, medium from cancerous cells, changes in pH, detergents and mechanical stress and treatment with TGFβ.
These studies suggest that ionizing radiation-induced bystander effects reflect a general stress response.
If confirmed, this then may have implications for the significance of bystander effects for low-dose radiation risk assessment in that ionizing radiation would be one of many factors affecting general stress responses.
It is particularly important to establish whether bystander-mediated effects are in general risk-enhancing or risk-reducing in respect of radiation-associated diseases.
ADAPTIVE RESPONSE- AR
• Small radiation doses have been also proven to reduce the impact of a subsequent, higher dose.
• This has been termed an adaptive response and is related to hypothetical mechanisms of hormesis.
• A low level of ionizing radiation (i.e. natural background radiation) might "immunize" cells against DNA damage (such as free radicals or larger doses of ionizing radiation), and decreases the risk of cancer.
• AR was demonstrated at various levels: molecular, cellular, tissue, whole animal, human (cellular)
AR AND LEUKEMIA
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Control mice have a life expectancy of 1000 d
Mice pre-exposed to 0,1 Gy and irradiated with 1 Gy have a life expectancy of 800 d
Mice pre-exposed to 0,1 Gy and irradiated with 1 Gy have a life
expectancy of 800 d
Mice irradiated with 1 Gy have a life expectancy of 600 d
Mitchel RE et al 1999
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Redpath et al. 2001
At very low doses, the transformation frequency is below that predicted by linear extrapolation
Linear Prediction of Transformation Actual Transformation
Sometimes a low radiation exposure of 1- 10 cGy, close to the yearly background level, appears to act as the “tickle”
dose, and reduces cancer rates.
CANCEROUS CELLS
• The beneficial effects vary from increased longevity, enhanced growth, increased embryo production, augmentation of
immune response to enhanced repair of cytogenetic damage
that protects against disease, effects that are not activated in
absence of ionizing radiation.
• Radiation hormesis in humans has been reported extensively in different radiation exposure groups ranging from:
• victims of atomic bomb, nuclear workers, radiologists and radiation technicians, patients, exposed to diagnostic radiation
and/or radiotherapy, flight crews and astronauts, and residents
living in a high background radiation environment.
AR IN HUMANS
The High Background Radiation Research Group (1980) from China compared an area with an average radiation exposure of 2.31 mSv/y to a similar area with 0.96 mSv/y, and reported that the cancer mortality rate was lower in the high background group.
A lower cancer death rate was also found in residents living in a high-altitude compared to a low-altitude environment.
Nambi & Soman (1987) showed an inverse correlation between background radiation levels and cancer incidence and mortality in India, and indicated that the annual cancer incidence rate decreased by 0.03/µSv increase in the external background radiation dose.
Mine et al. (1990) reported that among about 100,000 A-bomb survivors registered at Nagasaki Univ School of Medicine, 290 male (but not in female) subjects exposed to 500-1490 mGy showed significantly lower mortality from noncancerous diseases than age-matched unexposed males.
AR: EPIDEMIOLOGY STUDIES
ADAPTIVE RESPONSE- AR
The theory proposes that low levels of IR
activate cellular DNA-repair enzymes,
antioxidant mechanisms,
and immune surveillance.
RADIATION HORMESIS • Toxicology pioneer Paracelsus noted that
dangerous substances can be beneficial at low levels.
• All life on earth is continually exposed to low-level, ionizing-radiation stresses. Much harsher and more threatening radiation environments existed during our planet's early years, and mammals survived over billions of generations via a complex system of activated natural protection which includes DNA repair and anti-neoplastic immune surveillance.
• “Radiation hormesis’’ is the name given to this putative stimulatory/adaptive effects of low-level ionizing radiation (generally in the range of 1–50 cGy of low-LET radiation).
The activation of these networks may then result in net beneficial effects on the cell, organism, or species .
• Adaptive response may be useful in radiation therapy to protect normal tissue.
• Induction of repair genes may decrease the response to low-dose radiation.
• If adaptive response is demonstrated at low doses and dose-rates, it may have an impact on radiation protection standards.
IMPACT OF AR
LNT HYPOTHESIS IN THE LOW DOSES RANGE
• A: Increased risk for low doses (BE, GI).
• B:LNT.
• C: Decreased risk for low doses.
• D: U-shape hormetic curve (AR).
The LNT hypothesis states that:
• Any amount of radiation may pose an increased risk for causing cancer hereditary effects
• Risk is directly proportional to dose and without a threshold.
• Other variables are insignificant comparing to dose.
DIFFERENT HYPOTHESES ON RISK ESTIMATE
• At present, opposing hypotheses on the potential risks of low-dose radiation in humans are being debated because of their enormous impact on the health of current and future generations and their practical implications.
1. There is no dose of radiation that can be considered completely safe and that the use of radiation must always be determined on the basis of risk versus benefit (LNT model).
2. Due to bystander and genomic instability) risk from low-doses may be greater than that provided by the LNT model.
3. Health risks of doses less than 0,1 Gy are not measurable and may even be nonexistent (existence of threshold).
4. Low doses may be protective against exposure to environmental stressors by an hormetic mechanism.
• It has to be emphasized that different organisms, animal species, strains, organs, tissues, cells, molecules may respond
differently to the same kinds of radiation in the presence of
different backgrounds or experimental conditions.
• Therefore, there is a wide range of radiation doses used to induce hormesis, adaptive responses, radioresistance,
bystander effects, and genomic instability.
VARIABILITY IN RESPONSES TO LOW DOSES
• Exposures to high background radiation (mainly Uranium, Thorium, emitting α- particles ) at a low dose rate, 1.96 mSv/y (Yangjiang,
China)
• Japanese A-bomb survivors in Nagasaki (mainly γ-ray, neutrons) at higher doses of 500-1490 mGy.
• In C57BL/6 mice, by a single low dose of X-rays at 25 mGy
• Extremely low priming dose of X radiation at 0.001mGy X rays induced an adaptive response for chromosomal inversions in pKZ1 mouse
prostate
• γ-ray chronic irradiation at 1.5 Gy (0.001 Gy/min for 25 h) induced an adaptive response in the spleens of C57BL/6N mice.
DOSES INDUCING HORMESIS
The radiation dose for inducing bystander effect can be as low as
0.31mGy in Chinese hamster ovary cells irradiated in the G1 phase of the
cell cycle with alpha-particles from a plutonium-238 source (Nagasawa
andLittle, 1992)
or as high as 10 Gy for the lung of Sprague-Dawley rats exposed to 60Co
gamma rays (Khan et al 1998).
Genomic instability may be induced at a radiation dose as low as 0.5 Gy
using neutron whole-body irradiation in the haemopoietic cells of CBA/H
mice at 0.17Gy/ h.
or as high as 50 Gy in kidney cells from the radiosensitive BALB/c mouse
irradiated using a 137Cs irradiator at a dose rate of 6.70 Gy/min at 0°C
(Okayasu et al 2000).
DOSES INDUCING BE AND GI
Epigenetics is defined as heritable changes in gene activity and expression that occur without alteration in DNA sequence. Epigenetics is one of the fastest-growing areas of science and has now become a central issue in biological studies of development and disease Epigenetic mechanisms include:
Histone modifications, DNA methylation, Small and non-coding RNAs Chromatin architecture.
These mechanisms, in addition to other transcriptional regulationary events regulate gene activity and expression during development and differentiation, or in response to environmental stimuli
EPIGENETIC CHANGES
LOW DOSE RADIATION-INDUCED EPIGENETIC ALTERATIONS
In addition to inducing genetic mutations, there is concern
that low doses of IR may also alter the epigenome.
Such heritable effects early in life can result in phenotypes
that are either detrimental or potentially protective
against subsequent environmental exposures.
LOW DOSE RADIATION-INDUCED IN UTERO EPIGENETIC ALTERATIONS
In a paper published in The FASEB Journal (Bernal et al 2013), it was demonstrated that exposures to low-doses of ionizing radiation in utero can alter the epigenetic response of the agouti viable yellow (Avy) mouse. This alteration resulted in increased DNA methylation, which plays an important role for epigenetic gene regulation in development and disease. It also increased the frequency of offspring showing the agouti-brown coat color. The researchers also determined that that this response is in part dependent on a cellular oxidative stress response.
Low Dose Radiation-Induced Epigenetic Alterations Found in Agouti Mouse Model
• Exposures from 0.7 to 7.6 cGy significantly shifted the coat color distribution of the offspring toward brown.
• These mice have a lower frequency of obesity, diabetes, and cancer than those that are yellow, suggesting that low doses of radiation alter the epigenome in a way that is beneficial to the offspring in this mouse strain.
• Hypomethylation of DNA at high doses of radiation and hypermethylation at low doses indicates that the mechanisms of action are different as a function of radiation dose.
• This would suggest that the shape of the dose response for this response is nonlinear and would be sublinear in the low dose region
At the lowest exposure dose of 0.4 cGy, offspring coat color distribution was not significantly altered from that of sham-irradiated control offspring. In contrast, graded exposures from 0.7 to 7.6 cGy significantly shifted the coat color distribution of the offspring toward heavily mottled and brown. .
Low Dose Radiation-Induced Epigenetic Alterations Found in Agouti Mouse Model
IMPLICATIONS FOR ESTABLISHED VIEWS OF CANCER INITIATION
Conventional theories of radiation carcinogenesis are based on the single hit theory: a cell, mutated by a ionizing track, may initiate cancer.
This clonal origin of radiogenic cancer is used to calculate risk of cancer by relating risk to number of induced DSB.
Horizontal and vertical transmission of damage undermine the direct association of a DNA “hit” with development of a cancer and support instead the idea that radiation induces a field change which allows unstable cells to proliferate.
CHANGING THE LNT ASSUMPTION? NCRP, ICRP AND BEIR CONCLUSION
In 2001 the National Council on Radiation Protection and Measurements published NCRP Report No. 136. It presents an evaluation of the existing data on the dose–response relationships and current understanding of the health effects of low doses of ionising radiation.
In the ICRP Publication 99 and in the 2005 preliminary version of the BEIR VII report by the US National Academy of Sciences it is concluded that:
Although the available data do not exclude the existence of a universal low dose threshold, the evidence as a whole does not favour this proposition.
The conclusion of the report comes out in support of the continued use of LNT for radiological protection purposes.
CHANGING THE LNT ASSUMPTION?FRENCH ACADEMY OF SCIENCES CONCLUSIONS
• A diametrically opposed view has emerged from the French Academy of
Sciences and the National Academy of Medicine ( Dose–effect relationships and estimation of the carcinogenic effects of low doses of ionising radiation in French in late 2004 and in English in March 2005).
• LNT is considered to have been plausible scientific hypothesis in the 1960s, when cell defence mechanisms was largely unknown.
• Proportionality between dose and carcinogenic effects is plausible only if the effectiveness of defence mechanisms also remains constant irrespective of dose and dose rate while many studies demonstrated that at low doses the defence’s machinery works better.
• They believe that epidemiological studies have been unable to detect a significant increase of cancer incidence in humans for doses below about 100 mSv and state that:
The use of LNT for assessing the risks of doses below 20 mSv
is unjustified and should be discouraged.
THE IMPACT OF GENETIC SUSCEPTIBILITY
• Identification of sensitive subpopulations may suggest an increased risk at low doses for that subpopulation.
• Resistant individuals would have lower than average risk.
• Scientists are trying to find better ways to determine if someone is particularly sensitive to radiation.
• Understanding genetic susceptibility will help predict and control risk in clinical and occupational settings.
MANY THANKS FOR YOUR KIND ATTENTION!
