Chronic Low-Dose Radioactive Exposure: False Alarm or Public Health Hazard?

Wolfgang Koehnlein. Director of the Institute for Radiation Biology, University of Muenster, 48129 Muenster, Robert-Koch-Strasse 43, Germany and Rudi H. Nussbaum, Portland State University, Portland OR 97205-0751/USA

Ionizing radiation and its biological effects has been studied since more than one hundred years. One of the most important correlations to prove causality between absorbed radiation dose and observed effect is the Dose-Effect-Relation.
If the effect of a physical or chemical agent increases with dose, the agent can be considered as cause.
Besides the deterministic radiation effects at high doses, the stochastic effects at low doses have been studied most intensively in radiation research.
The predominant end points have been cancer induction and mutations. The former concerns the exposed person the latter his or her descendents.
It is therefore understandable that the question of the shape of the dose-effect curve became a very important point of discussion.
The question that worries us is: Is there a low dose or low dose rate of low LET radiation (beta, gamma or X-rays), that does not cause any additional cancer morbidity and any excess mutations in the exposed population and their offspring?
In other words: Is there any dose range above background up to a certain threshold without any detrimental effect?
If the idea of a safe dose and dose rate would become the prevailing scientific opinion, then the intended and unintended exposures could be allowed to increase above the present level.
Since 1927 the permitted dose levels have been reduced continiously (figure 1 and Table 1). This trent could then be reversed. If the idea of a safe and harmless dose would prevail, even if it is wrong, it would lead to an unnecessary increase of cancer cases and genetic defects worldwide.
Very much is at stake in considering the question of the existence of such a safe threshold-dose.
For any further discussion the term safe dose and safe dose rate have to be defined. A safe dose and safe dose rate of ionizing radiation means that all exposed persons remain unharmed during and after the exposure. Nobody will later on suffer from a radiation induced cancer or die prematurely from other radiogenic disease.
An unsafe dose or dose rate, on the other hand, means, that during exposure and afterward a certain fraction of the exposed will suffer from radiation induced cancer and will die prematurely, whereas the rest remains unharmed.
In the literature there are numerous statements of experts and expert commissions who consider the existence of a threshold dose with low LET radiation as real [1, 2, 3].

Some experts have expressed the opinion that the question whether a safe threshold dose exists can not be answered at present [4, 5]. In contrast, however, I belive that there exist to date sufficient data of exposed population which definitely show that there exists no safe dose, nor dose rate, thus no safe threshold [6, 7].
I will illustrate this conclusion with a few examples. There are, of course, also corresponding data from model systems which also show that there is no safe threshold dose [8, 9]. However, I would like to confine myself to observations made with exposed groups of people. My reasons are as follows:
1. Transfer of the results from model systems to human beings introduces an unnecessary uncertainty [10].
2. There are numerous published investigations on human beings exposed in the low dose range relevant for radiation protection [11, 12, 13, 14, 15, 16].

These are the starting points of my consideration:
1. The dose from low-LET ionizing radiation is delivered by high speed electrons (compton- and photoelectrons) traveling through human cells and creating primary ionization tracks. One such track is the least possible disturbance which can occur at the cellular level. A "high dose" means many tracks per cell; "low dose" means few tracks per cell; "low dose rate" means few tracks per cell per unit time. Whenever there is any dose at all, it means some cells and cell-nuclei are being transversed by ionizing tracks.
2. Radiation induced carcinogenic alterations mean alterations in the genetic material of the cell, the DNA. Cancer initiation is a unicellular process following the rules of chance. Every track independently of any other track has a chance of inducing cancer by creating such alterations. The energy deposited during a primary interaction is many times the chemical binding energy in organic molecules.

3. This implies that there can never be any dose or dose rate which does not cause primary damage. However, if every potentially carcinogenic alteration induced by tracks at low doses or low rates were successfully and invariably "undone" by repair processes, then there would be an inherently safe dose and dose rate. The key question is: Does repair of carcinogenic injuries operate flawlessly, when dose is sufficiently low and slow?

4. If a radiation dose is received within the time frame required for repair, and if repair would operate flawlessly and would leave no carcinogenic cellular damage, then the net effect of that radiation dose toward cancer-production would obviously be zero, by definition and many such small doses at rates comparable to the corresponding repair times would be absorbed without any increase in cancer rate.

5. Human epidemiological evidence shows, however, that repair fails to prevent radiation induced cancers, even at doses where the repair system has to deal with only one or a few tracks at a time and even at dose rates which allow ample time for repair before arrival of additional tracks (damage). By any reasonable standard such evidence is proof, that there exists no dose or dose rate which is safe.

Before I will discuss several examples from the epidemioIogical literature, I would like to comment on the number of primary ionisation tracks traversing a cell nucleus at a given dose.
In order to find out whether there is any safe dose it is apropriate to convert a given dose in fractions of Sievert into number of tracks through the cell nucleus since the smallest possible dose is not a fraction of a Gray but a single traversal of an ionizing track through the cell nucleus.
As we know the energy of x- and gamma-rays is deposited in biological material via photo- and Compton - electrons. One can, therefore, use the calculations of Paretzke and a recursion method [17] to convert the energy of a x- or gamma-ray into the number of electrons and their energy distribution. Thus, it is possible to convert the original photon energy to electrons and calculate their summarized range [18, 19].
With help of the relation 1cGy = 6,24 . 10¹⁰ keV/g one can now determine how many photons of a given energy are required to deposit a dose of 1 cGy. With this information the total sum of the electron tracks is obtained.
Since the average dimensions of a mammalian cell and its nucleus are known [20], we arrive at the number of nuclear traversals per dose unit for x- and gamma-radiation of different origin.

We know from numerous experiments with modelsystems, that enzymatic repair processes are working without impairment even at doses of a few Grays [21, 22, 23, 24, 25]. Furthermore it has been confirmed repeatedly in studies with human cells in vitro that whatever repair is achieved is mostly complete within 6 hours or less even after doses of several Grays [26, 27, 28, 29]. There is also confirmed information on the number and type of DNA lesions.

There are, however, numerous references in the literature that certain DNA-lesions are not repaired or are misrepaired. Some examples: The UNSCEAR-Report 1986 [30] states the following on repaired, unrepaired and misrepaired carcinogenic lesions induced by radiation: "The error-free repair of the DNA, the most likely target involved, leaves some fraction of the damage unrepaired and the error-prone repair may produce misrepaired sequences in the DNA-structure".
Kellerer describes a type of radiation induced DNA damage which would be difficult to repair [22]: "A simple example would be neighboring single-strand breaks in complementary strands of DNA, which interfere with excision repair". This is confirmed by Feinendegen et al. [27] who, reporting on irradiated cells, says "not all double-strand breaks are fully repaired".
With the information discussed so far, we can examine whether there is any safe dose or not.
Imagine the following scenario: The repair processes work flawlessly up to a certain dose of a few cSv (100 cSv = 1 Sv). A number of individuals are exposed to such a small dose on Monday. All induced lesions in the DNA are flawlessly repaired within a few hours. No increase of cancer risk results from this exposure. On Tuesday there is another exposure with the same small dose. Since the repair systems are working error free, there is no increase in cancer risk after the first two doses.
On the following days further dose fractions are given, and so on.
In this scenario the individuals could acumulate rather high doses in many small dose fractions. However, no increased cancer risk would be detectable in a long term follow up. Since it is known, that the same total dose given at once will increase the cancer risk, we would conclude that the given dose fractions are harmless and that a threshold dose and a safe dose rate would be real.
If, however, the long term follow-up studies reveal increased cancer incidence in the exposed population although they were exposed only to small dose fractions over long time periods, then we would have to conclude that the repair system is error-prone even at low doses. It would also follow that the assumption of a safe threshold dose is wrong. For a number of carefully carried out epidemiological studies of exposed persons which have been accepted in the scientific literature, the dose fractions or doses respectively and the derived number of tracks per cell nucleus per exposure are compiled in the table (Table 4). In all nine studies a statistically significant increase in cancer incidence was observed in the exposed population.

1. See Ref. 13; 2. see Ref. 11; 3. Boice JD, Monson RR, Rosenstein M. Cancer mortality in women after repeated fluoroscopic examinations of the chest, Journal of the Nat'l Cancer Institute 66, 863 - 867, 1981; 4. Miller AB, Howe GR, Sherman GJ, Lindsay JP, Yaffe MJ, Dinner PJ, Risch HA, Preston DL. Mortality from breast cancer after irradiation during fluoroscopic examinations in patients being treaded for tuberculo-sis, New England Journal of Medicine 321, 1285 - 1289, 1989; 5. Gilman EA, Kneale GW, Know EG, Stewart AM. Pregnancy X-rays and childhood cancers: Effects of exposure age and radiation dose. Journal Radiol. Protection 8, 3 - 8, 1988; 6. MacMahon B. Prenatal X-ray exposure and childhood cancer. Journal of the National Cancer Institute 28, 1173 - 1191, 1962; 7. see Ref. 15; 8. Harvey EB, Boice JD Jr., Honeyman M, Flannery JT. Prenatal X-ray exposure and childhood cancer in twins, New England Journal of Med. 312, 541 - 545, 1985; 9. see Ref. 11

These studies show that the following doses can not be regarded as safe with respect to cancer induction.
9 cSv, 7.5 cSv, 4.6 cSv, 1.6 cSv, 1 cSv, 0.9 cSv, 0.5 and even 0.1 cSv.

We can, therefore, conclude, whenever an ionizing track traverses a nucleus of a mammalian cell, there is always a chance that it will cause a carcinogenic lesion and that the lesion will be unrepaired, inherently unrepairable or misrepaired. In short, there is an inherent failure rate in the repair system.
For the essential stochastic end points of radiation damage (cancer induction and mutation) the idea of a safe threshold dose and of a safe dose range must, thus, be given up.
The proponents of threshhold doses and even hormetic effects will certainly argue, that there are many studies where no radiation effect was found by the authors. These studies are, however, unsuited for deciding whether there is a threshhold dose or not. This has also been admitted by the authors. Finding no significant effect can never be an argument for or against a safe dose. Very often the follow up periods were too short, the size of the cohorts too small or certain confounding factors were not taken into account properly.
A group of 12 independent scientists (physicians and epidemiologists) assembled and sponsored by Physicians for Social Responsibility have critically reviewed 124 epidemiological studies supported or financed by the U.S. DoE and the British Government [31]. Their eye opening report concludes among other things that:
1. ... the DOE*s epidemiological programme is seriously flawed...
2. ... the problems and flaws evident in many investigations are precisely those which tend to produce false negative results....
It is, therefore, no suprise that a large number of epidemiological mortality studies show no significant correlation between cancer induction and low dose radiation exposure.
The above micro-dosimetric analysis, combined with several independent epidemiological studies clearly show that the repair systems of the mammalian cell is never 100% perfect and that there is no harmless dose threshhold. That this has still not been accepted by most national and international commissions suggests that official radiogenic risk estimates are not based on exclusively scientific considerations but rather strongly influenced by political ones.

GENETIC EFFECTS OF RADIATION BY A-BOMBING

Dr. Hiroshi Maruya, Honorary Director of Hiroshima Kyohritsu Hospital, recently published a paper (Japanese Scientists, Vol.31. No.5., 1966) postulating that frequency of the outbreak of deformity has not been seriously taken up and that the genetic influence of A-bomb should not be ignored. The data quoted in the paper are copied below.