Part 1. Demolition of a Dream
In one critique of the First Edition (Skolnick 1995, p.367), the radiologist Dr. Stephen Feig suggests that low-dose diagnostic x-rays may be incapable of inducing any breast cancer. Feig asserts that any risk at all from mammography is "hypothetical" and, "With such low levels of radiation, there may be much less or even no risk."
If Dr. Feig were the only remaining distributor of the no-risk dream about low-dose radiation, we would not devote a chapter to it. But even some medical schools are still teaching radiologists that cancer-induction by diagnostic radiation is uncertain and just assumed. For example, the following statements come from the 1996 Radiology Syllabus for students at the University of California San Francisco Medical School (Goldberg 1996, p.129):
"High doses of ionizing radiation can produce breast cancer, but this has been demonstrated only at doses above 90 rads." (This claim, invalidated by several studies including the A-Bomb Study, also slipped into The Lancet, in Hulka 1995, p.885). The Syllabus adds: "There is absolutely no evidence ... that breast cancer is caused by mammography."
The no-risk, safe-dose dream about ionizing radiation has been powerfully demolished by three major analyses: NRPB 1995, UNSCEAR 1993, and Gofman 1990. (NRPB is Britain's National Radiological Protection Board; UNSCEAR is the United Nations Scientific Committee on the Effects of Atomic Radiation.) This chapter provides excerpts from all three. Because UNSCEAR and NRPB embrace much of the analysis in Gofman 1990, we will begin in Part 2 with Gofman 1990.
Does It Really Matter?
Part 2. Gofman 1990:
Proof There Is No Threshold Dose
or Dose-Rate
The no-risk speculation about low-dose radiation, illustrated at the outset of this chapter, has been tied for a long time to the fact that cell-nuclei have massive capacity to repair DNA damage (Chapter 42, Part 2). Once upon a time, nearly everyone (myself included) hoped that carcinogenic lesions might invariably be repaired --- correctly --- whenever the repair-system was not overwhelmed by "too much" radiation-induced damage all at once.
In the 1970s, however, it was already clear that perfect repair of injured human chromosomes did not occur, even when low total doses of radiation were received very slowly from weapons-testing fallout or chronic occupational exposures. And some evidence was already solid that radiation-induced human cancer is associated with very low doses and dose-rates. But might there be a safe dose (no-risk dose) at even lower levels?
Between 1970 and 1990, it was frequently asserted that the safe-dose issue could never be settled, because of the limits of epidemiology. In Gofman 1990, however, we were able to prove, by any reasonable standard of biomedical proof, that no safe dose or dose-rate exists with respect to radiation carcinogenesis.
The key breakthrough lies in recognizing that the relevant way to define the lowest possible dose and dose-rate of radiation is not in fractions of a rad. The relevant definition occurs in "tracks" per cell (Gofman 1971, pp.275-276; Gofman 1981, pp.405-411; Gofman 1986, pp.6-14). We will show why, by explaining "tracks" in Section 2a, below.
2a. The Least Possible Amount of Damage to Repair
- (1) "The dose from low-LET ionizing radiation is delivered
by high-speed electrons, traveling through human cells and creating
primary ionization tracks" (Gofman 1990,
p.18-2).
- (2) When genetic molecules are damaged by ionizing
radiation, each cell-nucleus attempts to un-do the damage by repair. The
damage done by a single primary ionization track is the least
possible damage which the repair-system ever can face. "Fractional
tracks do not exist. Either a track traverses a nucleus somewhere
(one nuclear track) or it does not (zero nuclear track)" (1990,
p.19-2).
- (3) "For disproof of any safe dose or dose-rate, it is more
important to establish the dose in terms of the average number of tracks
per nucleus, than to establish it in terms of rads. The reason is that
the lowest conceivable dose or dose-rate with respect to repair is not a
millionth or any other tiny fraction of a rad or centi-gray. The lowest
conceivable dose or dose-rate is one track per nucleus plus sufficient
time to repair it"
(1990, p.18-3,4).
- (4) "Because the minimal event in dose-delivery of ionizing
radiation is a single track, we can define the least possible disturbance
to a single cell-nucleus: It is the traversal of the nucleus by
just one primary ionization track" (1990,
p.19-1). The traversal is
complete in a tiny fraction of one second.
- (5) "Single, primary ionization-tracks, acting independently
of each other, are never innocuous with respect to creating carcinogenic
injuries in the cells which they traverse. Every track --- without help
from any other track --- has a chance of inducing cancer by creating such
injuries" (1990, p.18-2).
- (6) "... Any lesion which can be inflicted in a nucleus by a
pair of tracks, can also be inflicted by a single track acting
alone ... The earlier parts of this chapter leave no doubt that
events [injuries] at multiple, separate sites are certainly producible by
a single track, acting alone" (1990,
p.19-8).
2b. What Dose in Rads Delivers an Average of ONE Track / Nucleus?
- (7) Because a single primary track represents the least
possible challenge to the repair-system in a cell-nucleus, we
wanted to find out if there is solid human evidence of radiation-induced
cancer as a result of doses which deliver just one track or a few
tracks per nucleus. If such evidence exists, it indicates that repair
is not always perfect even when the challenge is about as low as
it can ever get. In other words, it would be direct evidence that
the hypothesis of a no-risk dose is false, with respect to
radiation-induced cancer.
- (8) So a necessary step in our analysis was figuring out
what dose in rads (cGy) delivers an average of ONE primary track per
cell-nucleus. Chapters 20,
32, and 33 in Gofman 1990 show how
such doses were derived, step-by-step. The doses vary with the
diameter of the cell-nucleus and with the energy of the radiation.
- (9) The values in the box apply to cell-nuclei with an
average diameter of 7.1 micrometers
(p.20-3). The
heading "Medical X-rays"
refers to diagnostic x-rays with an average energy of 30 KeV, generated
when the peak kilovoltage across the x-ray tube is 90 KeV. The heading
"596 KeV Gammas" refers to gamma rays from radium-226 and
daughters. Several additional sources of radiation are evaluated in
Tables 20-M and
20-"0" of
Gofman 1990.
Radiation Average number of Tissue-dose in
tracks per nucleus rads (centi-grays)
Medical X-rays 1 track 0.75 rad
10 tracks 7.48 rads
134 tracks 100.00 rads
596 KeV Gammas 1 track 0.34 rad
10 tracks 3.40 rads
294 tracks 100.00 rads
From Gofman 1990, Table 20-M.
- (10) When the AVERAGE number of primary tracks per nucleus is one, then:
37 percent of cell-nuclei experience no primary track at all;
37 percent of cell-nuclei experience one primary track;
18 percent of cell-nuclei experience two primary tracks;
6 percent of cell-nuclei experience three primary tracks;
1.5 percent of cell-nuclei experience four primary tracks;
Half-percent of cell-nuclei experience more than four primary tracks.
(From Table 20-N of
Gofman 1990).
2c. How Many Tracks at Once Can Overwhelm the Repair System?
- (11) In our 1990 analysis, we reviewed the existing
experimental evidence on what radiation doses are required to overwhelm
the repair-system for genetic molecules. In
Gofman 1990,
p.18-4,
we quote Albrecht Kellerer, one of the leading experts on the
issue:
"There is, at present, no experimental evidence for a reduction of the repair capacity or the rate of repair at doses of a few gray [a few hundred rads] which are relevant to cellular radiation effects" (Kellerer 1987, p.346). And: "There is little or no evidence for an impairment of enzymatic repair processes at doses of a few gray. Studies, for example by Virsik et al on chromosome aberrations, have established characteristic repair times that are substantially constant up to 10 Gy [1,000 rads], that is, up to the highest doses investigated" (Kellerer 1987, p.358).
- (12) We also reviewed the existing evidence on the time
required to finish repair (Gofman 1990,
Chapter 18). Numerous studies
indicate that cell-nuclei finish whatever repair they can perform on
genetic molecules within 3 to 6 hours, even after doses of 100 to 400
rads.
- (13) "The dazzling speed of repair has an extremely
important implication for settling the threshold issue. It means that
certain high-dose evidence can reveal a great deal, as we will
explain" (Gofman 1990,
p.18-5).
2d. Existing Human Evidence of Cancer from Minimal Doses
- (14) The relevant high-dose evidence comes from studies
of breast-cancer rates among women who received serial fluoroscopies
in the course of pneumo-thorax treatment for tuberculosis
(see Chapter 15
of this book, and see entries in the Reference
list for Boice 1977,
Boice 1978,
Boice 1981,
Boice 1991,
Howe 1984,
Hrubec 1989,
MacKenzie 1965,
Miller 1989,
Myrden + Hiltz 1969).
Because the women had so many fluoroscopic exams over months and years of treatment, their breasts accumulated radiation doses ranging from about 150 rads to over 1,000 rads (Gofman 1990, Chapter 21). But each exposure delivered single doses of 1.5 to 7.5 rads at a time. Such doses deliver, respectively, an average of just 2 or 10 tracks per cell-nucleus, as we see from paragraph 9 above.
- (15) These are very nearly the lowest possible
doses and dose-rates, with respect to challenging the repair-system
in a cell-nucleus. If the repair-capacity of cell-nuclei is not
overwhelmed by the tracks from hundreds of simultaneous rads
(paragraphs 11 and 12,
above), we can regard 10 tracks per nucleus, on the average, as
nearly minimal.
- (16) Referring to the Nova Scotia Fluoroscopy Study of
female tuberculosis patients, we wrote (1990,
p.21-2):
"If carcinogenic injury was produced in the irradiated women at their first fluoroscopy exposure-session, but if repair-systems were able to perform flawless repair afterwards, then that particular exposure-session would have left no residual harm, in terms of any increased risk of future breast-cancer." And:
"Similar carcinogenic injury inflicted at every subsequent fluoroscopy session would also have been without residual harm, if a flawless repair-system operated at a total dose per exposure-session of 7.5 rads. And thus, after accumulating 850 rads in this fashion, the irradiated women would have had no radiation-induced breast-cancer." And:
"The Nova Scotia Study is certainly not a high-dose study; at every critical step along the way, it is a test of how perfectly the repair-system can un-do carcinogenic injury produced by 7.5 rads, or 10 nuclear tracks on the average --- a low dose and dose-rate." Between exposures, ample time elapsed for completion of repair-work (paragraph 12).
- (17) The repair-system failed the test, conclusively,
not only in the Nova Scotia series of women, but also in additional
pneumo-thorax series in Canada and in Massachusetts. The evidence of
excess breast-cancer in the fluoroscoped women is very solid, and shows a
positive dose-response. This evidence of radiation-induced human cancer
is widely acknowledged and cited, but not many people recognize that it
shows repair-failure even after a challenge which was
minimal.
- (18) Our disproof of any threshold dose or dose-rate includes
six additional studies from the mainstream literature which show
radiation-induced cancer when the average number of tracks per cell-nucleus
ranged from 0.3 track to 12 tracks (Gofman
1990,
Table 21-A). They are the Israeli
Scalp-Irradiation Study (Modan 1977,
1989); the Stewart In-Utero
Studies (1956, 1958,
1970); MacMahon's In-Utero Study
(1962); the British Luminizer
Study (Baverstock 1981, 1983, 1987);
Harvey's In-Utero Study of Twins
(1985); Modan's Study of
Breast-Cancer in the Scalp Irradiation Study
(1989). The evidence against any
threshold embraces infants in-utero, children, adolescents, young women,
high-energy gamma rays, medical x-rays, acute single doses, acute serial
doses, and chronic occupational doses.
- (19) "In recent years, it has been fashionable to suggest
that epidemiologic investigations can not usefully address the low-dose
radiation question. The epidemiologic studies described here make it
apparent that this is incorrect ... When the effort is made to evaluate
the doses in such studies, in terms of tracks-per-nucleus, then it becomes
evident that studies whose doses are not `next-to-zero' are nonetheless
studies of truly minimal doses and dose-rates"
(Gofman 1990,
p.21-19).
2e. Failure of Repair: "The Troublesome Trio"
- (20) It is the combination of epidemiology with
track-analysis which reveals that we already know that (a) repair has
failures even when the repair-system has the least possible challenge,
and (b) the failure has cancer consequences. We do not need
impossible-to-obtain studies at doses like 10 milli-rads or 10
micro-rads --- because the least possible challenge to the
repair-system occurs at much higher doses.
- (21) "One can look with awe, humility, and gratitude
at a system of repair with the capacities demonstrated by the DNA
repair-system. But an independent analyst, or a realist of any
stripe, does not casually dismiss the troublesome trio: Unrepaired
lesions. Unrepairable lesions. Misrepaired lesions" (1990,
p.18-6). And:
"One cannot fault the repair-system in cell-nuclei for leaving a relatively small number of injuries unrepaired, or misrepaired, or for having some inherent inability to repair every conceivable type of injury inflicted at random by the tracks of high-speed electrons ... " (1990, p.18-6)
- (22) "... the human epidemiological evidence on dose
versus cancer-response provides no support for the speculation that
repair makes each rad less carcinogenic as dose falls. If that
were the net result of repair, the shape of dose-response would be
concave-upward. But what is seen in the A-Bomb Study and in
others is not concavity-upward. The finding is either
supra-linearity or linearity --- both of which are inconsistent with
the speculation that repair processes make each rad less carcinogenic
as dose and dose-rate fall" (1990,
p.18-6, 18-7).
- (23) "Our entire experience with human radiation
carcinogenesis should have made it evident that the problem we might
be facing is that --- regardless of dose-level --- some fraction of
radiation injury to nuclei is unrepaired ... some fraction is
unrepairable ... and some fraction is misrepaired" (1990,
p.18-7).
2f. Not "Hypothetical": Fatal Cancers from Minimal Doses
- (24) "The radiation-induced cancers arising from the
unrepaired lesions at low doses do not wear a little flag
identifying them as any different from cancers induced by higher
doses of radiation, or induced by causes entirely unrelated to
radiation. Therefore, threshold proponents cannot argue that the
cancers arising from the lowest conceivable doses of radiation will
somehow be eliminated by the immune system or any other bodily
defenses against cancer. Such an argument would require the
elimination of cancer in general by such defenses. Instead, we
observe that cancer is a major killer ... So the proposition would
lead to a non-credible consequence, and must be rejected" (Gofman
1990, p.18-2).
- (25) What about the speculation that low radiation doses
may induce a net health benefit, by stimulating DNA repair or by
stimulating the immune system? "When excess fatal cancer is observed
in humans after such exposures [minimal doses and dose-rates], the
excess has occurred despite any possible stimulation of the
repair- and immune-responses by low-doses. The net result is
injury, not benefit. I wish it were otherwise" (1990,
p.18-2).
- (26) "By reasonable standards of proof, the safe-dose
hypothesis is not merely implausible --- it is disproven ... We
conclude with a warning: Disproof of any safe dose or dose-rate
means that fatal cancers from minimal doses and dose-rates of ionizing
radiation are not imaginary. They are really occurring in exposed
populations. Proposals, to declare that they need not be considered,
have health implications extending far beyond the radiation
issue ..." (1990, p.18-18).
Part 3. UNSCEAR 1993: "Highly Unlikely That a Dose-Threshold Exists"
UNSCEAR 1993, written by the United Nations Scientific Committee on the Effects of Atomic Radiation, is a 922-page report (with no index) which presents a lot of valuable information and analysis.
Although authors of its nine big sections (called "annexes") are not identified, the total international membership of the Committee is identified on page 29. The biggest delegations are from Canada (9), China (7), France (9), Germany (7), Japan (11), Russian Federation (12), United States (11). Staff and consultants are identified on page 30.
Pagination in the report is consecutive from beginning to end, but paragraph numbers start over with each annex. Below, we will separate the page number and the paragraph number by a slash.
- (27) In its introduction, the report states: "The combination of epidemiology
and radiobiology, particularly at the molecular and cellular levels, is a useful tool for
elucidating the consequences of low doses of radiation" (1993, p.27/184). That very
combination is the essence of our proof, above, that there is no threshold dose with
respect to radiation carcinogenesis.
- (28) UNSCEAR also affirms our premise in paragraph 24, when it states:
"Epidemiological studies of human groups exposed to low-LET radiation show that a
range of neoplasms are represented in excess and, broadly, that these do not differ
markedly from those arising spontaneously in the population ... no unique neoplastic
signature of human radiation exposure is, as yet, apparent" (p.578/153).
3a. The Smallest Possible "Insult" at the Cellular Level
- (29) UNSCEAR 1993, like Gofman, recognizes the importance of using an
appropriate definition of the lowest possible radiation dose or dose-rate. And it
embraces our "microdosimetric approach to defining low doses and low dose rates"
(p.680/321):
"Photons deposit energy in cells in the form of tracks, comprising ionizations and excitations from energetic electrons, and the smallest insult each cell can receive is the energy deposited from one electron entering or being set in motion within a cell." See paragraphs 1-4 above.
- (30) The only conversion offered by UNSCEAR between tracks
and dose in rads (centi-grays) is for cobalt-60, which produces a far
more energetic gamma ray than the 596 KeV gammas presented above in our
paragraph 9. Says UNSCEAR (p.680/321):
"For cobalt-60 gamma rays and a spherical cell (or nucleus) assumed to be 8 micrometers in diameter, there is an average of one track per cell (or nucleus) when the absorbed dose is about 1 mGy [0.1 cGy or rad]. The dose, corresponding to one track per cell, on average, varies inversely with volume and is also dependent on radiation quality, being much larger for high-LET radiation."
- (31) At page 696, UNSCEAR supplies Table 17, "Proportion
of a cell population traversed by tracks at various levels of track
density." It is like Table 20-N in Gofman
1990. For instance, it shows what percentage of cells experience 0, 1, 2, 3, 4, and
more tracks per cell-nucleus, when the average track density is ONE track per
cell-nucleus. The percentages are the same as we show in paragraph
10, above.
- (32) The UNSCEAR authors define the region of "definite"
single-track action as the dose-region where not more than two
percent of the cell-nuclei experience more than a single track. "In
this dose-region, there are so few radiation tracks that a single cell
(or nucleus) is very unlikely to be traversed by more than one track"
(p.628/42). For cobalt-60, the two-percent criterion means a tissue-dose
of 0.2 mGy. Two percent is an arbitrary choice which seems completely
unrelated to the repair-issue --- even though UNSCEAR agrees with us that
the repair-issue is a critical part of the threshold-issue, as we will
show. However, after choosing cobalt-60 and a dose of only 0.2 mGy (20
milli-rads), the UN authors are correct in saying that there are no
corresponding human or animal data (p.628/42).
3b. UNSCEAR: The Carcinogenic Potency of a Single Track
- (33) "The most basic, although not sufficient, condition for a true dose
threshold is that any single track of the radiation should be totally unable to produce the
effect" (p.630/54).
- (34) "Radiation is able to induce a diversity of genomic lesions, ranging from
damage to single bases to gross DNA deletions and rearrangements" (p.578/153).
And: "Biophysical analyses based on Monte Carlo simulations of track structure show clearly that all types of ionizing radiation should be capable of producing, by single-track action, a variety of damage to DNA, including double-strand breaks alone or in combination with associated damage to the DNA and adjacent proteins" (p.632/63).
And: "In all these mechanistic models, a single radiation track from any radiation is capable of producing the full damage and hence the cellular effect" (p.632/64).
- (35) "There is compelling evidence that most, if not all, cancers originate
from damage to single cells ... Point mutations and chromosomal damage play roles in the
initiation of neoplasia" (p.8/37).
And: "Single changes in the cell genetic code are usually insufficient to result in a fully transformed cell capable of leading to cancer; a series of several mutations (perhaps two to seven) is required ... The whole process is called multi-stage carcinogenesis" (p.8/38). And: "It is possible that radiation acts at several stages in multi-stage carcinogenesis, but its principal role seems to be in the initial conversion of normal stem cells to an initiated, pre-neoplastic state" (p.8/39).
- (36) "... the majority of neoplasms originate from damage to single cells. In
principle, therefore, the traversal of a single target cell by one ionizing track from
radiation has a finite probability, albeit low, of initiating neoplastic change" (p.556/26).
- (37) Our topic here is real-world human evidence relating
to the threshold-issue for radiation-induced cancer. We omit unrelated
references by UNSCEAR to dose-response curves induced in various
experiments, although we are interested in such experiments
(see Gofman 1990,
Chapter 23). With respect to the
threshold-issue, we quote UNSCEAR:
"Multi-stage models of carcinogenesis could lead to expectations of a dose threshold, or a response with no linear term, under particular, highly restricted sets of assumptions" (p.636/84). But, "it would be difficult to conclude on theoretical grounds that a true threshold should be expected even from multi-stage mechanisms of carcinogenesis, unless there were clear evidence that it was necessary for more than one time-separated change to be caused by radiation alone" (p.633/69).
3c. UNSCEAR: Does "Repair" Deliver a Threshold Dose?
A threshold-dose for radiation-induced cancer is a dose below which there is no risk of radiation-induced cancer. A safe dose.
- (38) As long as there are any primary tracks at all
occurring in a biological tissue, a radiation dose is occurring. UNSCEAR
acknowledges that "the dose and dose-rate region of main practical
relevance in radiation protection (0-50 mSv per year) [0-5 rems per
year] is characterized by small average numbers of tracks per cell with
long intervals of time between them. Effects are, therefore, likely to
be dominated by individual tracks, acting alone" (p.628/43). This is
precisely the point made in Gofman
1990, p.20-7).
- (39) "Cells are able to repair both single- and
double-strand breaks in DNA over a period of a few hours, but
sometimes misrepair can occur" (p.625/28).
- (40) "The extent to which radiation-induced DNA damage
may be correctly repaired at very low doses and very low dose rates
is beyond the resolution of current experimental techniques. If DNA
double-strand breaks are critical lesions determining a range of
cellular responses, including perhaps neoplastic transformation, then
it may be that wholly accurate cellular repair is unlikely even at
the very low lesion abundance expected after low dose and low-dose-rate
irradiation" (p.634/74).
- (41) "It is highly unlikely that a dose threshold exists
for the initial molecular damage to DNA, because a single track from
any ionizing radiation has a finite probability of producing a sizable
cluster of atomic damage directly in, or near, the DNA. Only if the
resulting molecular damage, plus any additional associated damage from
the same track, were always repaired with total efficiency could there
be any possibility of a dose threshold for consequent cellular
effects" (p.636/84).
- (42) "Biological effects are believed to arise
predominantly from residual DNA changes that originate from radiation
damage to chromosomal DNA. It is the repair response of the cell that
determines its fate. The majority of damage is repaired, but it is
the remaining unrepaired or misrepaired damage that is then considered
responsible for cell killing, chromosomal aberrations, mutations,
transformations and cancerous changes" (p.680-681/323).
Part 4. NRPB 1995: Evidence "Falls Decisively" against a Threshold
In October 1995, Britain's National Radiological Protection Board released a 77-page report entitled "Risk of Radiation-Induced Cancer at Low Doses and Dose Rates for Radiation Protection Purposes" (NRPB 1995). Its five authors are Cox, Muirhead, Stather, Edwards, and Little.
- (43) Chapter 2 of NRPB 1995 reviews the existing
human epidemiologic evidence and concludes (p.25/61): "It is
important to note that the studies of low-LET exposure considered
in this chapter are consistent with a linear trend in cancer
risks at low doses without threshold." This statement embraces
the pneumothorax-fluoroscopy studies (p.13/23).
- (44) Chapter 5 of NRPB 1995 reviews "Cellular and
molecular mechanisms of radiation tumorigenesis." There, the
authors also state the now-familiar definition of the lowest
possible dose and dose-rate from ionizing radiation:
"It may be argued ... that a single radiation track (the lowest dose and dose rate possible) traversing the nucleus of an appropriate target cell, has a finite probability, albeit low, of generating the specific damage that will result in tumour-initiating mutation" p.58/27).
- (45) The authors consider existing evidence
relating to the reduction of radiation risk by so-called
cellular "adaptive" responses and immune-system responses. In
particular, they discuss issues raised in
UNSCEAR 1993 and in
UNSCEAR 1994 (Annex
B). The authors reach the same conclusion that we
do: Such cellular responses do not provide any
threshold dose with respect to post-repair genetic
damage. NRPB concludes (p.75/21):
"Whilst adaptive responses or other protective mechanisms may influence the risk of tumour development, they do not provide a sound basis for judgement that tumorigenic response at low doses and low dose rates of radiation is likely to have a non-linear component which might result in a dose threshold below which the risk may approach zero."
4a. NRPB on Special Difficulties in Repairing Radiation Damage
The NRPB authors understand very well that failure of repair is the key to the absence of any threshold dose. The following excerpts from their 1995 report show they understand that ionizing radiation has the power to induce some unrepairable damage to chromosomes and DNA, and that a difference exists between action by primary ionization tracks, and action by the free radicals which are produced by normal cellular metabolism (see p.292 of this book).
- (46) "Radiation-induced damage to DNA nucleotide
bases and to the sugar-phosphate backbone on one strand of the
DNA duplex closely resembles the cellular damage that occurs
through normal endogenous metabolic processes" (p.59/28).
"It is generally accepted that, in the absence of exogenous agents, each cell in the human body sustains 5,000 to 10,000 DNA damage events per hour [they cite Ames 1989 and Billen 1990], principally as a consequence of thermodynamic instability and attack by chemical radicals produced via endogenous biochemical reactions; this damage is believed to contribute to natural cancer risk" (p.59/29).
- (47) "On this basis, arguments have been made
[they cite Billen 1990 and
Abelson 1994] that the
small increment of additional cellular DNA damage resulting from
low dose radiation exposure will have an insignificant effect
on the frequency of gene and chromosomal mutations, and by
implication, on cancer risk. This would be a valid hypothesis
if the DNA damage resulting from spontaneous endogenous
processes were to be identical with that induced by
ionising radiation. There is, however, strong evidence that
this is not the case and, consequently, that the hypothesis
lacks credibility" (p.59/30).
- (48) "The vast majority of endogenous DNA
lesions takes the form of DNA base damage, base losses,
and breaks to one of the sugar-phosphate backbone strands of
the duplex. Such single-strand DNA damage may be
reconstituted rapidly in an error-free fashion by cellular
repair processes ..." (p.59/31).
- (49) "In contrast, although a single ionising
track of radiation will also induce single-strand damage when
an energy-loss event takes place in close proximity to one
DNA strand, a cluster of such loss events within the diameter
of the DNA duplex, of about 2 nanometers, has a significant
probability of simultaneously inducing coincident damage to
both strands. In support of this, an approximately linear
dose-response for double-strand break induction by low-LET
radiation is observed, confirming that breakage of
both strands of the duplex may be achieved by the
traversal of a single ionising track and does not
demand multiple-track action ..." (p.59/32).
And:
"There is also evidence that a proportion of radiation-induced double-strand breaks are complex and involve local multiply damaged sites --- LMDS [they cite Ward 1991-a] ..." (p.59/32).
- (49) "A given fraction of radiation-inducible
double-strand damage will be repaired efficiently and correctly,
but error-free repair of all such damage even at the low
abundance expected after low dose exposure should not be
anticipated" (p.60/33). And:
"Unlike damage to a single-strand of the DNA duplex, a proportion of double-strand lesions --- perhaps that component represented by LMDS --- will result in loss of DNA coding from both strands. Such losses are inherently difficult to repair correctly, and it is believed that misrepair of such DNA double-strand lesions is the crucial factor underlying the induction of chromosomal aberrations and gene deletions that represent the principal hallmarks of stable mutations induced by ionising radiation of various qualities" (p.60/33). And:
"Double-strand DNA losses may in principle be repaired correctly by DNA recombination, but there is evidence that radiation-induced DNA damage may be subject to error-prone illegitimate DNA recombination which can result in the forms of gene and chromosomal mutations that are known to characterise malignant development" (p.60/33).
- (50) "The importance of DNA double-strand
damage and its repair for the radiation response of cells is
further supported by studies indicating, firstly, that the
repair of such damage is the principal determinant of dose
and dose-rate effects after low-LET radiation and, secondly,
that genetically determined cellular radiosensitivity is
predominantly associated with deficiencies in DNA
double-strand break repair. Finally, there is evidence that
it is the difference in the quality and not the
quantity of induced DNA double-strand lesions that
principally provide for the increased biological effectiveness
of high-LET radiation such as alpha particles compared with
low-LET radiation such as x-rays and gamma rays; these
observations are best explained by experimental and
computational data indicating that, overall, DNA double-strand
lesions in cells induced by high-LET radiation are more complex
and less likely to be repaired correctly than those induced
by low-LET radiation ..." (p.60/34).
- (51) "In summary, a coherent argument may be
assembled that at low doses and low dose rates of low-LET
radiation, DNA single-strand damage either is repaired in
an error-free fashion or is an insignificant component of
tumour risk. For double-strand DNA damage, there is good
reason to believe that repair has an error-prone mutagenic
component irrespective of damage-abundance and, by
implication, will, even at very low doses, contribute to
tumour risk" (p.60/36).
- (52) "It may be concluded ... that existing
data from both in vitro and in vivo [radiation] studies
support a linear rather than a threshold-type response for
neoplasia-initiating gene mutations" (p.61/38).
4b. NRPB's Conclusion on a Threshold Dose
- (53) "It is concluded ... that data relating
to the role of gene mutations in tumorigenesis, the monoclonal
origin of tumours, and the relationship between DNA damage
repair, gene/chromosomal mutation and neoplasia are well
established and broadly consistent with the thesis that, at
low doses and low dose rates, the risk of induced neoplasia
rises as a simple function of dose and does not have a DNA
damage or DNA repair related threshold-like
component" (p.75/21). And:
- (54) The following statement by the NRPB authors
is remarkably similar to paragraph 26 above:
"In consideration of a broad body of relevant cellular and molecular data, it is concluded that the weight of the evidence, in respect of the induction of the majority of common human tumours, falls decisively in favor of the thesis that, at low doses and low dose rates, tumorigenic risk rises as a simple function of dose without a low dose interval within which risk may be discounted" (p.68/80).
Comment:
In view of parts 2, 3, and 4 of this chapter, we hope that editors at JAMA, Lancet, and elsewhere will stop helping to distribute the deadly safe-dose fallacy.