Linear no threshold theory-pdf

It is commonly stated that “any radiation dose, no matter how
small, can cause cancer.” The basis for that statement is the linear-
no threshold theory (LNT)–which might more appropriately be
called “linear-no threshold hypothesis”—of radiation carcino-
genesis. According to LNT, if a 1 Gy (100 rad) dose gives a cancer
risk R, the risk from a dose of 0.01 Gy (1 rad) is R/100, the risk from
0.00001 Gy (1 millirad) is R/100,000, and so on. Thus the cancer
riskisnotzeroregardlessofhow smallthedose.
However, over the past several years, many radiation health
scientists have come to regard risk estimates in the low-dose region
based on LNT as exaggerated or completely negligible. For
example, the 6,000-member Health Physics Society, the principal
organization for radiation protection scientists, issued a position
paper stating: “Below 10 rad…risks of health effects are either too
small to be observed or are nonexistent.” A similar position
statement was issued by the American Nuclear Society. When the
asked for submission of
comments on validity of LNT, there were about 20 negative
comments submitted and only a single comment supportive of
LNT. In a worldwide poll conducted by the principal on-line
discussion group of radiation protection professionals
(RADSAFE), the vote was 118 to 12 against LNT. A 2001 Report
by the French Academy of Medicine concluded that LNT is
“without any scientific validity,” and an elaborate joint study by the
French Academy of Medicine and the French Academy of
Sciences stronglycondemnedtheuseofLNT.
While U.S. official agencies have been slower to accept this
position,the U.S. National Council on Radiation Protection and
Measurements (NCRP) stated in NCRPPublication No. 121: “Few
experimental studies and essentially no human data can be said to
prove or even provide direct support for the [LNT] concept,” and in
NCRP Publication No. 136 stated: “It is important to note that the
rates of cancer in most populations exposed to low-level radiation
have not been found to be detectably increased, and in most cases
the rates appear to be decreased.”Agroup of scientists opposing use
of LNT (Radiation Science and Health) submitted several hundred
paperssupportingtheirpositiontotheNationalResearchCouncil.
Beyond failure of LNT, there is substantial evidence that low-
level radiation may be against cancer; a view known as
“radiation hormesis.” There is a society, formerly called the
International Hormesis Society, now known as the International
Dose-Response Society, which sponsors an annual international
scientific conference and publishes a peer-reviewed scientific
journal and a regular newsletter,
.
Previous reviews with somewhat different approaches to
similar objectives, have also reviewed the basis for LNT and
informationthathascausedashiftinviews.
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Health Physics Society Newsletter
protective
BELLE: Biological Effects of Low
LevelExposures
Foundation fortheLinear-NoThreshold Hypothesis Challenged
The original basis for LNT, as it emerged in the mid-20
century, was theoretical and very simple. A single particle of
radiation hitting a single DNA molecule in a single cell nucleus of
the human body can initiate a cancer. The probability of such a
cancer initiation is therefore assumed to be proportional to the
number of such hits, which is proportional to the number of
particles of radiation, which is proportional to the dose. Thus the
riskisproportionaltothedose—thisistheLNT.
An important problem with this simple argument is that factors
other than initiating events affect the cancer risk. Human bodies
have biological defense mechanisms that prevent the vast majority
of initiating events from developing into a fatal cancer. Some of the
most important examples, as summarized by Feinendegen, include:
induction of DNA repair enzymes; apoptosis, a process by which
damaged cells “commit suicide”; immune system stimulation; and
delaying mitosis and thus extending the time before it occurs,
during which damage repair is most effective. Low-level and high-
levelradiationhaveoppositeeffectsontheseprocesses.
By far the most important cause of DNA damage is reactive
oxygen species(ROS). Elevationof ROS stimulatesthescavenging
processes that remove them by initiating biochemical reactions that
are stress responses. Thus, “the best protection against stress is
stress itself.” These scavenging processes are enhanced by low-
levelradiation.
Altered cell timing affects DNA repair in many ways. Other
effects of low-level radiation on cell survival have been observed
and are referred to as “low-dose hypersensitivity,” “increased
radiationradioresistance,”and“death-inducingeffects.”
It is now recognized that development of cancer is a much more
complex process than was originally envisioned. The role of
“bystander effects,” signaling between neighboring cells relevant
to their radiation experiences, is now recognized to be an
important, albeit poorly understood factor. In fact it seems that
tissue response, and even whole organ response, rather than just
cellularresponse,mustbeconsidered.
There is also apparently obvious evidence for failure of the
original simple model. For example, the number of initiating events
is roughly proportional to the mass of the animal—more DNA
targets mean more hits. Thus the simple theory predicts that the
cancer risk should be approximately proportional to the mass of the
animal. But the cancer risk in a given radiation field is similar for a
30 g mouse and a 70,000 g human. As another example, our very
definition of dose, based on the energy absorbed per unit mass of
tissue, which is proportional to the number of radiation hits per unit
target mass, would be misleading if only the total number of hits
(which is proportional to the number of initiating events) were
relevantregardlessofthetargetmass.
A detailed theoretical approach to evaluating the validity of
LNT is based on the commonly accepted idea that double-strand
th
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Bernard L. Cohen, Ph.D.
The Linear No-Threshold Theory of
Radiation Carcinogenesis
Should Be Rejected
Journal of American Physicians and Surgeons Volume 13 Number 3 Fall 200870

breaks (DSB) in DNAmolecules are the principal initiating event in
causing cancer. But DSB are also caused by endogenous ROS. (In
fact the main mechanism for radiation-induced DNAdamage is the
production of ROS by the ionizing effects of the radiation on
omnipresent water.) It is estimated that endogenous ROS cause
about 0.1 DSB per cell per day, whereas 100 mSv (10 rem) of
radiation, which is close to the upper limit of what is normally
called low-level radiation, causes about 4 DSB per cell. Assuming
that the number of cancers is proportional to the number of DSB, a
100 mSv dose of radiation would increase the lifetime (28,000 days
x 0.1 DSB/day) risk of cancer by only about 4/2,800 (0.14%),
whereasLNTpredictsanincreaseof1%.
A direct demonstration of the failure of the basis for LNT
derives from microarray studies determining what genes are up-
regulated and down-regulated by radiation. It is found that different
sets of genes are affected by low-level radiation than by a high-level
dose. For example, in one study of mouse brain, 191 genes were
affected by a dose of 0.1 Sv but not by a dose of 2.0 Sv, 213 genes
were affected by 2.0 Sv but not by 0.1 Sv, while 299 genes were
affected by both doses. The 0.1 Sv dose induced expression of
genes involved in protective and repair functions, while down-
modulatinggenesinvolvedinunrelatedprocesses.
A similar study with even lower doses on human fibroblast
cells found that a dose of 0.02 Sv caused more than 100 genes to
change their expression, and these were generally different from
the genes affected by 0.5 Sv. The former group was heavily
weightedbystress responsegenes.
Several other microarray studies have shown that high radiation
doses that serve as the calibration for application of LNT are not
equivalenttoanaccumulationoflowradiationdoses.
Sophisticated experimentaltechniques have been developed for
observing the effects of a single alpha particle hitting a single cell. It
was found that the probability for transformation to malignancy
from N particle hits on a cell is much greater than N times the
probability for transformation to malignancy from a single hit. This
is a direct violation of LNT, indicating that estimated effects based
on extrapolating the risk from high exposure, represented by N hits,
greatly exaggerates the risk from low-level exposure as represented
byasinglehit.
A very clear demonstration of a threshold response, in contrast
to LNT, was found in tumor induction by irradiation throughout life
of mouse skin. For irradiation rates of 1.5 Gy/wk, 2.2 Gy/wk, and
3 Gy/wk, the percentage of mice that developed tumors was 0%,
35%,and100%,respectively.
According to the biological defense mechanism called the
“adaptive response,” which was described by UNSCEAR,
exposing a cell to a stress such as radiation stimulates natural
defense and thereby protects against subsequent further stresses.
Experimentally, this is most easily studied by exposing cells to a low
dose to prime the adaptive response, followed by a “challenge dose,”
andcomparing theresponsetothatofthechallengedosealone.
Radiation exposure increases the number of chromosome
aberrations, the simplest tool for detecting genetic damage. Table 1
shows how a priming low dose decreases radiation-induced
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DirectExperimentalChallenges totheLNT
TheAdaptive Response
aberrations in human lymphocyte cells in vitro. An in vivo
experiment in mice found that the chromosome aberrations induced
by 65 cGy (65 rad) fell from 38% to 19.5% in bone marrow cells
and from 12.6% to 8.4% of spermatocytes when a priming dose of
0.2cGywas administered3hours earlier.
Many other such experiments have been reported, and the
results are usually explained as production of repair enzymes by the
primingdose.
The effects of human exposure were studied in lymphocytes
taken from residents of a high background radiation area (1 cGy/y)
and those of a normal background radiation area (0.1 cGy/y) in Iran.
After exposure to 1.5 Gy (150 rad), the mean frequency of
chromosome aberrations was 0.098 ± 0.012 for cells from the high-
background group compared to 0.176 ± 0.017 for cells from the
normal-backgroundgroup,adifferenceof4standarddeviations.
In a microarray study on human lymphoblastoid cells, in which
a 0.05 Sv priming dose was followed by a 2.0 Sv challenge dose,
145 genes were affected by the priming dose. Generally, genes
affecting protein synthesis were up-regulated, and those involved in
metabolic processes and signal transduction were down-regulated,
perhaps as a means of conserving resources needed for DNArepair.
The specifics were quite complex and sometimes pointed in
different directions; for example, the TP53 gene plays an important
roleboth as atumor promoter and suppressor.
One in vitro study of genetic mutations found that the
frequency of mutations at the locus in human lymphocytes was
reduced from 15.5 x 10 to 5.2 x 10 when an X-ray exposure of 300
cGy was preceded 16 hours earlier by an exposure to 1 cGy. Other
examples of adaptive response have been reported from studies of
geneticmutations.
Apriming dose of 2 cGy before a pre-mating dose of 200 cGy of
X-rays consistently reduced dominant lethal mutations in
byhalf.
In addition to protecting against a large challenge dose, low-
dose radiation protects against spontaneous malignant
transformation in predisposed cells. Spontaneous neoplastic
transformation was reduced by 78% in C3H 10T1/2 mouse cells,
and by 55% in human HeLa x skin fibroblast cells. The effect is
statisticallysignificantevenatverylowdoses, below1cGy.
This adaptive response protection against spontaneous cancers
probably results from reducing ROS and increasing the
antioxidants that remove them. In a study of rat cells, 50 cGy of X-
ray exposure decreased the amount of the oxidant lipid peroxide by
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hprt
Drosophila
Table 1. ChromosomeAberrations. Two types of chromosome aberrations in
human lymphocytes induced by 400 cGy of X-rays, either alone or 6 hr after
pre-exposure to 5 cGy.18
Dicentrics & Rings Deletions
DONOR 400 cGy (5 + 400) cGy 400 cGy (5+400)cGy
#1 136 92 52 51
#2 178 120 62 46
#3 79 50 39 15
#4 172 42 46 34
#5 134 106 58 41
Journal of American Physicians and Surgeons Volume 13 Number 3 Fall 2008 71

about 20%, and increased the amount of the antioxidant enzyme
superoxide dismutase (SOD) by about 25%. These beneficial
effects were appreciable over the entire dose range up to above 100
cGy. Many other studies with similar results have been summarized
byYukawa.
The immune system destroys cells with persistent DNA damage
and is thus important in protecting against the development of
cancer. The effects of low-level radiation on several different
measures of the immune response are listed in Table 2. We see that
by each of these measures, the immune response is increased by low-
level radiation, and increasingly so at least up to 7.5 cSv. Responses
over a wide range of radiation doses show that the stimulatory
effects atlow levels arereversedathighdoses ofradiation.
Contrary to expectations from the basic assumption of LNTthat
the cancer risk depends only on total dose, effects on the immune
system are very different for the same total dose given at low dose
rate vs. high dose rate. In a study of effects on various indicators of
immune response in several wild-type mouse strains, continuous
whole-body irradiation at 1.2 mGy/hr stimulated immune response,
butthesamedoses givenatahighratehadtheoppositeeffect.
In a study of thymic lymphomas in mice, acute challenge
doses totaling 7.2 Gy induced tumors in 90% of the mice, but if the
mice were previously exposed at a rate of 1.2 mGy per hour for 258
days (a total of 7.2 Gy), only 43% developed such tumors. Note that
the total priming dose is equal to the challenge dose. The difference
is in the low dose rate. Even extending the low-dose-rate exposure
to 450 days for a total exposure of 12.6 Gy resulted in no tumors
without a challenging dose. Various indicators of immune response
were significantly increased by the continuous whole-body
radiation, and the authors attribute their results to this stimulation of
theimmunesystem.
Several studies have shown that the immune system provides
resistance to metastasis of tumors. For example, when tumor cells
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StimulationoftheImmune System
TheEffectofDose Rate
are transplanted into the groins of mice, the rate of their metastasis
into the lung is cut about in half by total-body irradiation with
15–30 cGy 12 days after the transplantation. Doses above 50 cGy,
on the other hand, reduce the immune response, leading to
increased rates of metastasis. A study in rats showed that total-
body irradiation—but not tumor irradiation—with low-level
radiation reduces the rate of metastasis and increases infiltration
intothetumorofimmune-systemagents.
Studies on naturally cancer-prone mice found that, while low-
level radiation exposure does not prevent eventual development of
cancer, it delays the process substantially. Total-body irradiation
with low-level radiation has also been shown to reduce tumor
size. The only reasonable explanation for such effects of total-
body low-level radiation would seem to be stimulation of the
body’s immunesystem.
There have been numerous direct studies of cancer risk vs. dose
in animals, testing the validity of LNT. Nearly all of these studies
indicate, with high statistical significance, that LNT overestimates
the cancer risk from low-level radiation, generally suggesting a
threshold. In a study at Oak Ridge National Laboratory, the LNT
not only failed in the low-dose region, but animals exposed to low
doses lived up to 40% longer than controls. A review of more than
100 such experiments involved a total of 85,000 exposed animals
with their 45,000 corresponding controls, with a total of 60,000 and
12,000 cancers in exposed and control animals respectively. In
cases where cancers were observed in control animals, either no
effect or an apparent reduction in cancer risk was observed in 40%
of the data sets for neutron exposure, 50% of the data sets for X-
rays, 53% of the data sets for gamma rays, and 61% of the data sets
foralphaparticles.
The principal human data cited by those in influential positions
to support LNT are those for solid tumors (all cancers except
leukemia) among the Japanese A-bomb survivors. The data do
indeed suggest a linear relationship with the intercept near zero
dose. But when error bars are considered, they give no statistically
significant indication of excess cancers for doses below about 25
cSv. This conclusion applies to the incidence data as well as to the
mortality data. In fact, it was shown that considering the three
lowest dose points alone (i.e. up to 20 cSv), the slope of the dose-
response curve has a 20% probability of being negative (risk
decreasing with increasing dose). A later update of the data on A-
bomb survivors has been published, but with insufficient detail to
repeat the above analysis. A crude preliminary analysis indicates
thattheaboveconclusionswillnotbeappreciablychanged.
The data on leukemia among A-bomb survivors strongly
suggest a threshold above 20 cSv, and this difference from LNT
expectations is recognized by the authors and by all widely
recognizedreviews.
The principal other evidence that has been widely cited as
supporting LNT is the IARC (InternationalAssociation for Research
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Experimentaland ObservationalStudies of
CancerRisk vs. Dose
AnimalStudies
AtomicBomb Survivors
Studies ofMonitoredRadiationWorkers
Table 2. Effects of Radiation on Immune Response. Percent response to
various tests in mice exposed to indicated dose compared to response of
unexposed mice.
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Test 2.5 cGy 5 cGy 7.5cGy
PFC Reaction 110 143 174
MLC Reaction 109 133 122
Reaction to Con A 191 155 530
NK activity 112 109 119
ADCC Activity 109 128 132
PFC = plaque forming cell; MLC = mixed lymphocyte culture, used as test of
T-cell function; ConA= concanavalin-A, lectin that stimulates T-lymphocytes;
NK = natural killer cells which recognize and kill tumor cells; ADCC =
antibody-dependent cell-mediated cytotoxicity, which assists NK activity.

on Cancer) studies of monitored radiation workers.The first and most
fully reported was a study of 95,673 monitored radiation workers in
the United States, United Kingdom, and Canada. For all cancers
except leukemia, there were 3,830 deaths but no excess over the
number expected. The risk is reported as -0.07/Sv (90% confidence
limits.-0.04 , +0.3).Thereis surelynosupportforLNThere.
However, for the 146 leukemia deaths, a positive risk-vs.-dose
relationship was reported and was vociferously claimed to support
LNT.The data are listed inTable 3. It is obvious from those data that
there is no indication of any excess risk below 40 cSv; even the
excess for >40 cSv is by only 1.4 standard deviations. The
conclusion by the authors that this supports LNT is based on an
analysis that arbitrarily discards the data in Table 3 for which O/E
(observed/expected) is less than unity! That means that three of the
sevendatapointsarearbitrarilydiscarded.
For a follow-up study by the same group, involving 407,000
monitored workers in 154 facilities spread through 15 countries,
results were reported only as excess risk per Sv, assuming LNT.Thus a
data display similar to that in Table 3 cannot be given here, but since
the lead author is the same, it seems reasonable to assume that similar
questionable procedures were used. No information on smoking
status, an important risk factor for cancer, was collected. No
consideration was given to nonoccupational exposure; the average
occupational exposure was 2 cSv, and 90% were below 5 cSv, where-
as theaverageperson is exposedthroughoutlifetoabout25cSv of non-
occupational radiation with large variations, typically at least 10 cSv,
depending on geography and medical treatment. Thus the “signal” is
very much smaller than the noise, making any conclusions about
validity of LNThighly debatable.Another weakness is that most of the
data were derived from photographic film badges, which are sensitive
to humidity and temperature. The films were handled differently in the
15 different countries (and also frequently by different organizations in
the same country), reducing the reliability of the results. There are
other inherent problems in combining data from many different
sources, such as differences in ethnicity and socioeconomic status. If
the data from just one of the 15 countries, Canada, are excluded, the
excess risk is no longer statistically differentfromzero.
Many other studies have been reported on cancer risk vs. dose
for normal occupational exposures. In response to heavy media
coverage of some nonscientific reporting, a $10 million study
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was carried out by the U.S. Centers for Disease Control and
Prevention (CDC) of workers in eight U.S. Navy shipyards
involved in servicing nuclear-propelled ships.The study included
28,000 exposed workers and 33,000 age- and job-matched
controls who worked on non-nuclear ships. The former group all
had exposures above 0.5 cSv and average exposures of 5 cSv. The
cancer mortality rate for the exposed was only 85% of that for the
unexposed, a difference of nearly two standard deviations. Hiring
procedures, medical surveillance, job type, and other factors were
the same for both groups; the study was specifically designed to
eliminate the “healthy worker effect,” which is often used to
explain such results. The issue of nonoccupational exposure was
not addressed, but there was a high degree of homogeneity among
thedifferentworker groups being compared.
When mortality rates for employed workers are compared with
those for the general population, it is invariably found that
employed workers have lower mortality. This is widely understood
to result from the fact that unemployed persons may be unemployed
because of health problems that may cause their earlier demise.
However, the healthy worker effect should not apply to cancers
occurring long after their initial employment, because health
problems leading to such cancers would not be apparent in a pre-
employment medical examination. A direct test of this in
Sweden, comparing 545,000 employed women with 1,600,000
unemployed women found that the standardized cancer incidence
rate for employed women was 1.05 (95% confidence interval [CI],
1.03-1.07) times higher than for the unemployed women. This
would certainly seemto eliminatehealthy worker effects forcancer.
Several other studies of cancer rates among people whose
employmentinvolvesradiationexposurehavebeenpublished:
British radiologists who began work in earlier years, when
exposure standards were much more lax than today, had excess
cancers compared to other medical practitioners. But among the
most recent cohort, radiologists who began work between 1955 and
1979, cancer mortality was only 0.71 (95% CI, 0.49–1.00) times
that of other medical practitioners, who presumably had
considerablylowerradiationexposures.
A study of Chinese medical workers, comparing those exposed
with those not exposed to X-rays, showed a relative risk of cancer
incidence of 2.4 for leukemias and 1.2 for solid tumors in earlier
workers whose average exposure was 55 cGy. For more recent
workers, with average exposures of 8.2 cGy, the RR was not
significantlydifferentfrom1.0.
A U.S. study of 146,000 radiologic technologists reported a
standardized mortality ratio (SMR) of 0.82 for all cancers,
compared with the total U.S. population, but there was a
statistically significant increase among those first employed before
1940,comparedwiththosewho beganwork after1960.
A review of studies of eight cohorts of radiologists and
radiological technologists in various countries, comprising
270,000 monitored radiation workers, concluded that there was
good evidence for excess cancers among the early workers, but no
suchevidenceamongmorerecentworkers.
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Among 22,000 monitored workers in the French nuclear power
industry, the cancer mortality rate was only 0.58 (90% CI,
0.49–0.68) times that for the general population of France. The
authors attribute this to the healthy worker effect, but this seems to be
an unlikely explanation for such a large effect.There was no evidence
forincreasedcanceras afunctionofincreasingradiationexposure.
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Table 3. Leukemia deaths from IARC Study. The final column is the ratio of
observed to expected, O/E.
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Dose (cSv) Observed Expected O/E
0-1 72 75.7 0.95
1-2 23 21.2 1.08
2-5 20 21.8 0.92
5-10 12 11.3 1.06
10-20 9 7.8 1.15
20-40 4 5.5 0.73
>40 6 2.6 2.3

Perhaps the most reasonable conclusion from studies of
normally exposed radiation workers is that they give no conclusive
information on effects of low-level radiation. There is as much
information suggesting zero or negative risk as information
indicating the increased risk claimed by the IARC study. In any
case, the fact that the monitored radiation received by the subjects
was much lower than their nonoccupational unmonitored
exposures,makethesedatainherentlyofmarginalsignificance.
There is a substantial, statistically robust collection of human
datacontradictorytoLNT.Thesearesomeexamples:
Canadian women exposed to frequent fluoroscopic
examinations in a tuberculosis sanatorium seemed to have a
decreased risk of breast cancer with increasing doses up to at least
25cSv,althoughstatisticaluncertaintiesaresubstantial.
Lung cancer data from these same Canadian women, and also
from a study of 10,000 individuals in Massachusetts, suggest a
decreasing risk with increasing dose in the low-dose region, in this
case extending at least up to 100 cSv, and no statistically significant
increased risk up to 350 cSv.This is drastically inconsistent with the
data for Japanese A-bomb survivors for whom the risk seems to
increase linearly with dose up to 300 cSv, where it is three times the
zero-dose risk.There are many factors to be considered in the bomb
survivors, one being the high dose rate from the bomb compared
with the protracted fluoroscopic examinations extending over
manyweeks.
In 1957, an explosion in a mismanaged radioactive waste
storage facility at the U.S.S.R. Mayak nuclear weapons complex in
the Eastern Urals of Siberia caused large radiation exposures to
people in nearby villages. A follow-up on 7,852 of these villagers
found that the rate of subsequent cancer mortality was much lower
among these than among unexposed villagers in the same area. The
ratio ± one standard deviation for exposed to unexposed was 0.73 ±
0.07for4cGy,0.61±0.07for12cGy,and0.72±0.12for50cGy.
Studies are underway on the workers at this Mayak complex,
among whom there have been many excess cancers, but exposures
were generally quite high and the data reported give little information
onthedose-responserelationshipinthelow-doseregion.
Stimulation of the immune system by low-level radiation is
being used on an experimental basis for medical treatment of non-
Hodgkin’s lymphoma with total-body and half-body (trunk only)
irradiation. This radiation was administered to one group of
patients (“irradiated” group), but not to an otherwise similar
“control” group, before both groups were given similar other
standard treatments such as chemotherapy with or without
accompanying high radiation doses to tumors. In one such study,
50% of the control group, but only 16% of the irradiated group had
died after 9 years. In a much earlier study with different standard
treatment, 4-year survival was 70% for the irradiated group versus
40% for the controls. In another study in that time period with a
more advanced chemotherapy, 4-year survival was 74% for the
irradiated group versus 52% for the control group. Despite
information supportive of using whole-body or half-body low-level
radiation to stimulate the immune system, U.S. physicians have not
utilizedit.Furtherapplications,however,areunderwayinJapan.
Further work is needed on the effects of radiation-contaminated
buildings in Taiwan, where 10,000 occupants were exposed for up
to 20 years to an average of 40 cSv total. Among these, 232 cancer
OtherHuman Data
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deaths would be expected from natural causes plus 70 additional
deaths expected from LNT, but only seven cancer deaths have
occurred. Differences in the age distribution of the affected people
as compared with the general population have not been carefully
investigated, but preliminary estimates are that this might reduce
the expected number of cancers by about 20%, a change that would
not affect the conclusions. It would seem to be very important to
conduct a full epidemiological study of this situation, but the
funding agencies have not been cooperative despite heavy
pressures fromsegmentsofthescientificcommunity.
In addition to the data described above for X-rays, gamma rays,
and some neutrons for bomb survivors, there are also impressive
relevant data from radiation with alpha particles. One such study is
of bone and head cancers among dial painters, chemists, and others
occupationally exposed to ingested radium. There were no tumors
among those with exposures below 1,000 cGy; however, 25% to
38% in each category developed cancers for dose ranges centered
about 1,800 cGy; 3,500 cGy; 7,500 cGy; and 20,000 cGy. Elaborate
analyses of these data shows that an LNT fit is statistically
unsupportableandathresholdbehaviorisstronglysuggested.
Several studies have reported that workers who inhaled
plutonium, resulting in sizable radiation exposures to their lungs,
have lung cancer mortality rates equal to or lower than those not
thusexposed.
A study of lung cancer mortality rate as a function of average
indoor radon exposure showed a clear, statistically indisputable
tendency for lung cancer mortality to with increasing
radon exposure, with or without correction for smoking prevalence.
These data have been analyzed for more than 500 possible
confounding factors, including socioeconomic, geographic,
environmental, and ethnic associations, and the possible effects of
an unrecognized confounding factor were investigated, but the
conclusion remains firm that LNT fails decisively by grossly over-
estimatingthecancerriskfromlow-levelradiation.
Alpha Exposures
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decrease
A pooled analysis of seven case-control studies has been
interpreted as being in conflict with the above results. Its data are
listed in Table 4. Note that none of the data points show a
statistically significant excess lung cancer risk. The pattern
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Table 4. Odds Ratios for Lung Cancer vs. Residential Radon Exposure from
Seven Pooled Case-control Studies
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150-199 1.22 (0.87-1.71)
>199 1.37 (0.98-1.92)
Radon level (Bq/m3) Odds ratio (95% C.I.)
<25 1.00
25-49 1.13 (0.95-1.35)
50-74 1.09 (0.89-1.34)
75-99 1.16 (0.91-1.48)
100-149 1.24 (0.96-1.60)

suggests an excess risk from radon exposures, although it does not
necessarily increase with dose, at least for the four lowest points that
comprise the region of significance in the Cohen study. A pooled
study includes many complicated adjustments for differences
among the various studies in the pool, and potential confounding
factors with the adjustments for the few of them that are recognized
might be a problem. In any case, the results in Table 4 cannot be
interpretedas atestofLNT.
A substantial body of data, both on animals and on humans,
indicates that the time delay between radiation exposure and cancer
death increases with decreasing exposure. These observations
lead to the obvious conclusion that for low enough exposures, this
time delay exceeds the normal life span, so no actual cancers
develop.Thus,thereisaneffectivethreshold.
This effect alone, even in the absence of all considerations
discussed previously in this paper, would invalidate LNTas applied
tolow-levelradiation.
The conclusion from the evidence reviewed in this paper and
more extensively elsewhere is that the linear-no threshold theory
(LNT) fails very badly in the low-dose region, grossly over-
estimating the risk from low-level radiation. This means that the
cancer risk from the vast majority of normally encountered
radiation exposures is much lower than given by usual estimates,
andmaywellbezeroorevennegative.
Dependence ofLatentPeriodon Dose
68, 69
70
Conclusion
Bernard L. Cohen, Ph.D.,
Acknowledgement:
is a professor of physics and of environmental
and occupational health, University of Pittsburgh. Contact: blc@pitt.edu.
The author acknowledges a great debt to Myron
Pollycove and James Muckerheide for help in pointing out references
involved in this paper, and to Jane Orient for help in its preparation.
This paper is adapted from a chapter by B.L. Cohen, “The cancer risk
from low-level radiation” in Tack D, Gevenois PA, eds.
Berlin: Springer-Verlag; 2007, with the kind permission of
Springer Science and Business Media.
Medical Radiology
Radiation Dose from Pediatric and Adult Multidetector Computed
Tomography.
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