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RADIATION HORMESIS

Biopositive Effect of Radiations

 

1 - Introduction

2 - Development of the Hormesis Concept

3 - Acute expozure to ionizing radiation
4 - Chronic Exposure to Ionizing Radiation

5 - Discution of Radiation Hormesis in cancer Mortality
6 - Compare and Contrast Hormesis and Homeopathy
7 - Radiation Hormesis is Essential

 

T.D. LUCKEY

1009 Sitka Ct, Loveland, CO 80538, USA

 

 

 

1. Introduction

 

My purpose is to promote harmony with nature and to improve our quality of life with the knowledge that cancer mortality rates decrease following exposure to low dose irradiation. Hormesis (Greek HORMO = I excite) is the stimulation of any system by low doses of any agent. Hormology is the study of excitation. Low doses of many agents evoke a biopositive effect ; large doses produce a bionegative effect. The message is simple : small and large doses induce opposite physiologic results.

             Radiation hormesis implies stimulation by ionizing radiation. Cancer induction is the most feared action of large doses of ionizing radiation. Therefore, cancer mortality rates will be used to illustrate radiation hormesis in humans. Large doses of ionizing radiation increase cancer mortality rates ; this is considered to be harmful. Since small doses decrease cancer mortality rates, low dose irradiation is beneficial. Although small doses of radiation can stimulate cell an cancer growth, the stimulation of different components of our complex immune system more than compensates for simple cellular effects. The net effect is a decreased cancer mortality.

             This report will a) review the development of the concept of hormesis, b) present an overview of radiation hormesis in humans, c) compare and contrast hormesis and homeopathy, and d) suggest a surprising mechanism. Constraints of time and space dictate that each of these will be very brief.

 

 

2. Development of the Hormesis Concept

 

 Antibiotics became available to non-medical investigators toward the end of World War II. It was just 50 years ago that I received some streptomycin from the Eli Lilly Company. Our working hypothesis was : feeding antibiotics should prevent intestinal microbes from supplying unknown vitamins to the host ; the animal should then exhibit a new vitamin deficiency. The expected did not happen ; chicks fed streptomycin grew better than controls (Moore et al, 1946). The mechanism of action of dietary antibiotics was complex (Luckey, 1959). The use of germfree animals showed that part of the action was directly on the host ; part was on the intestinal microbes (Luckey et al, 1956). This began the use of dietary antibiotics for animals all over the world.

             A literature search revealed much information suggesting that large and small doses evoke opposite effects : Hippocrates, Similia similibus curentur or "likes are cured by likes" ; Paracelsus, the father of infinitesimal doses, "The dose makes the poison" ; Hahnemann, "Drugs have a dynamic effect when used in small doses" ; Cannon, "Adaptation to perturbations is the basis for homeostasis" ; Selye, "The General Adaptation Syndrome" ; and Arndt-Schultz, "Poisons are stimulants in small doses". These were supported by the remarkable findings of Richet (1906). He understood the oligodynamic action of metals as proposed by Nageli (1893) : very dilute solutions of metallic ions are toxic. Richet quantified the toxic effects by using serial dilutions of several metallic ions. He found that each metal ion exhibited a threshold and was stimulatory at subharmful doses. This linked out antibiotic response to classic science.

             Hormesis was the word suggested by Southam and Erlich (1943) who determined the effective concentration of phenolic compounds in wood which protects trees from fungi decay. They diluted their extracts to determine the minimum amount needed for fungal retardation. The unexpected increase in growth rate with dilute solutions was called hormesis. They agreed to a broad definition of the word.

 

 

Figure 1. Summary of the effects of chronic, whole body exposures on four physiologic functions. Radiation hormesis is represented by the defined area above the horizontal line. When compared with the controls, represented by the horizontal line, large dose rates exert a negative effect.

  

 

             Many physiologic functions show radiation hormesis : growth, neuromuscular development, hearing and visual acuity, learning and memory, fecundity, immune competence, cancer mortality and average lifespan (Luckey, 1990; 1993). The effects of chronic, whole body exposure to low doses of ionizing radiation upon four physiologic functions shows radiation hormesis (Figure 1). The controls, at ambient levels of radiation, are set at one, the horizontal line. Hormesis is displayed by values >1. Large doses decrease these functions. There is a definite threshold, the zero equivalent point (ZEP), at the transition between biopositive to bionegative effects. Note that the ZEP is more than 1,000 times ambient radiation levels. Note also that cancer mortality is displayed as an inverse function : the less cancer mortality, the higher the relative value.

             The results from human experiences are grouped near ambient levels of radiation (Figure 1). Results from animal experiments comprise the large group of results on the right side. Since these were more than 100 times ambient levels of radiation, the two components leave a gap in our knowledge about low dose irradiation, an area for future research. When both chronic and acute exposures were considered, over 100 experiments showed statistically valid, p<0.01, radiation hormesis. There is no comparable set of results which show harm from low dose irradiation (Luckey, 1990; 1993). The results displayed in figure 1 provide background for this critical review of recent literature on cancer mortality in humans exposed to whole body irradiation.

 

 

3. Acute Exposure to Ionizing Radiation

               

Acute exposure to ionizing radiation is exemplified by the 86,520 Japanese survivors of atomic explosions ; 41,372 were in the exposed cohort (Shimizu et al., 1992).

The total cancer mortality and leukemia mortality rates of lightly exposed survivors were consistently less than that of the control population (Figure 2).

             The chisquare statistic indicates that these data are not significant because the sample size is too small. If the sample size were to be increased by a factor of ten, the data would show statistically significant decreased mortality rates for both total cancer and leukemia in the lightly exposed population, p<0.01.

             Radiation hormesis in cancer mortality was found in 32,000 United States and 22,000 British military observers of atmospheric nuclear explosions (Robinette et al., 1985; Darby et al., 1988). The cancer mortality rate of Canadian military observers was only 88% of carefully selected military controls (Raman et al., 1987). The leukemia mortality rate of the Canadian observers was only 40% of that of the unexposed controls. In each study the cancer motality rate of exposed personnel was lower that that of the general population.

             The cumulative data represents about 100,000 acutely exposed persons in four countries. This is convincing evidence that whole body exposure to low doses of ionizing radiation do not cause increased mortality. The supporting animal data showed that both acute and chronic exposure to low dose irradiation decreased cancer mortality (Luckey 1990, 1993). The combined animal and human results provide impressive evidence that cancer mortality is decreased by acute exposure to low doses of ionizing radiation.

 

 

4. Chronic Exposure to Ionizing Radiation

 

Chronic whole body exposure to ionizing radiation is pertinent to the welfare of all societies. Epidemiologic studies of chronic exposure to ionizing radiation consistently showed a negative correlation between ambient (background) radiation and leukemia, cancer and total mortality rates (Luckey 1990, 1993). These are exemplified by a study in which lung cancer mortality rates were compared with radon in homes (Figure 3) (Cohen, 1993). The dashed line represents a popular fallacy. Unfortunately, many agencies use this erroneous concept for official recommendations and regulations. The solid line represents the mean values, with 5% errors bars, from 1700 counties of the United States in which 90% of the population reside. The negative slope of the solid line shows that the optimun concentration must be greater than the 4 pCi l-1 which some agencies consider to be excessive. Cohen's data confirm the results of Haynes from England and Wales (Haynes, 1988). Large radon clinics in Russia are used to treat a variety of minor disease problems (Bogoljubov, 1988).  

 

            

Figure 2. Cumulative mortality rates in Japanese survivors of atomic bombs (Shimizu et al., 1992) The numbers above the abscissa give the thousands of persons exposed to all doses up to and including the dose indicated: A: cumulative total cancer mortality rate and B: cumulative leukemia mortality rates.

 

 

            

             When the concentrations of radon and progeny were increased to over one million times ambient levels, lung tumors were induced in animals. This is not cause to change our perception of the results in figure 2. Low levels of radon and progeny do not cause lung cancer mortality ; they may decrease it.

             Chronic exposure to low dose irradiation is exemplified by nuclear workers. A summary of recent studies in over 7,000,000 person-years of exposed nuclear workers is given in Table 1. In most studies there was a significantly lower cancer mortality rate in exposed workers than in unexposed workers in the same plants, p<0.05-0.001. Only in the smallest study was the difference not significant. It is suggested that this study had inadequate correction for age.

             Leukemia is the classic radiation-induced cancer. The leukemia mortality rates of 130,000 exposed workers was less than that of unexposed workers, p<0.01 (Gilbert et al., 1989; Abbatt et al., 1983; Gribbin et al., 1993; Kendall et al., 1992).

 

 

 

 

 

                            

Figure 3. Lung cancer mortality rates in males compared with radon concentration in United States homes (Cohen, 1993). Each mean ± one standard deviation includes the number of counties represented. The dashed line indicates the invalid, but much used, linear model of the data.

 

 

Presumably, low dose irradiation activates the immune system to destroy the altered stem cells of leukemia. This concept is supported by many studies showing increased activity of the components of the immune system (Sugahara et al., 1992)

 

 

 

 

 

 

 

 

 

TABLE 1. Total cancer mortality in nuclear workers

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   Plant                                         Worker                                            % Cancer

                                 Control                          Exposeda                        Mortalityb

US Shipyardsc           32,510                            38,220                                   67*  Matanoski

US Weapons             20,619                            15,817                                   21** Gilbert

Canada Energy          21,000                              4,000                                   59** Abbatt

Canada Energy           4,000                              4,000                                   95*   Gribbin

Brit.Weapons            24,500                            70,900                                    3** Kendall

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*  P< 0.05         ** P< 0.001                                                                           

a Lifetime exposures were 1-20 cSv.

b % = Exposed/internal Control X 100.

c Total death rate ; total cancer mortality data were not found.

 

5. Discussion of Radiation Hormesis in Cancer Mortality

 

Most evidence showed a significant decrease in cancer mortality rates of lightly exposed humans. This was true for acute exposures, survivors of atomic bombs in Japan and observers of atmospheric nuclear explosions in the United States, Britain and Canada. It was equally true for chronically exposed workers when compared with eiter unexposed workers in the same plants or with the general population. The obvious conclusion is : low doses of ionizing radiation do not cause cancer. Experimental animals show the same result (Luckey 1990, 1993). Thus, it is highly probable that low dose irradiation actually lowers cancer mortality rates in humans.

             Radiation hormesis is used with success in the clinic (Yamaha et al., 1992). The best results appear following irradiation of the lower body with 10-15 cGy twice weekly. This procedure is particularly useful in treating non-Hodgkin's lymphoma patients. Obviously, this opens the way for more clinical research.

             The evidence provides a new and scientifically valid concept; cancer mortality rates are lowered by exposure to low doses of ionizing radiation. This invalidates the zero thesis that all radiation is harmful. The use of linear, no threshold models should cease.

             Since most studies had internal controls, the results were not due to "a healthy worker effect". The "healthy worker effect" can not explain the decreased cancer mortality in nuclear workers. Most of the studies compared exposed workers with unexposed workers ; both a) were in the same plants, b) passed the same entrance examinations and c) had comparable medical care. Secondly, there is evidence that the exposed workers have a longer average lifespan. Since cancer mortality increases dramatically with age, the exposed workers should have had a higher cancer mortality rate than the controls. They did not. Thus, the best explanation for the decreased cancer mortality following low dose irradiation is radiation hormesis. These results negate the "healthy worker effect" and show that the use of linear, no threshold models for the effects of low dose irradiation is counterproductive.

 

 

6. Compare and Contrast Hormesis and Homeopathy

 

How can comparisons and contrasts between radiation hormesis and homeopathy be made ? One represents science ; the other the art of medicine. Science does not intrude on the delicate nuances between physician and patient. Science attempts to simplify and separate elements of complex phenomena. Medicine accepts the complex, ever changing condition of each patient as the progress of disease and multiple treatments acrue. Science demands strict controls and knowledge from multiple sources. Medicine involves individual faith, hope, beliefs and prayers in addition to all that science can contribute.

             Comparisons and contrasts of hormesis and homeopathy are listed in Table 2. Shared characteristics are listed in part A. Characteristics of homeopathy which do not typify hormesis are listed in part B. And hormesis characteristics not found in homeopathy are listed in part C. The major difference is that hormesis is a general phenomenon while homeopathy involves one, or very few, specific compounds for each malady. Many agents evoke hormesis. And each agent activates many systems ; hormetins stimulate reproduction, growth, neuromuscular develoment, mental acuity and memory, defense from infection and cancer mortality, and average lifespan. Radiation in cancer mortality is a lifetime effect ; most homeopathic treatments involve only a few day or weeks.

 

7. Radiation Hormesis is Essential

 

Finally, radiation hormesis is in a special class of hormetics. A major mechanism of action of ionizing radiation is proposed. It is probably an essential agent. Thus, radiation hormesis is comparable to those essential nutrients which are not present in adequate quantities in certain environments. The hormesis curve for ionizing radiation is comparable with those for vitamin A or selenium. An excess is harmful. Small amounts are needed for essential physiologic functions. Supplementation is usual for populations living in a partial deficiency. This is done for vitamin A and selenium. Irradiation supplementation promises increased quality of life and a new plane of health for people in the 21st century.

 

 

 

TABLE 2. Comparison and contrast of hormesis

and homeopathy

_______________________________________

 

A. Hormesis and Homeopathy are comparable

 

  Large doses are harmful

  Dose rate is important

  Low doses are beneficial

  Unusual compounds may be active

  Reaction initiated within hours

_______________________________________

 

B. Homeopathy characteristics

(not typical of hormesis)

 

  Only special compounds are active

  Very minute doses are active

  First dose sensitizes the subject

  Medical use is primary

  Psychosomatic factor is great

  Primary effects are short-lived

_______________________________________

 

C. Hormesis characteristics

(minimal in homeopathy)

 

  Non specific agents are active

  Medium doses are active

  Most dose rates are active

  Animal and human react

  Statistically valid data

  Many parameters are affected*

  Immune competence involved

  Benefits sick and well

  Effective for months/years

  Public health concern

 

* Fecundity, development, lifespan

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             New concepts raise new questions. What is an optimal level of radon, alpha, beta, gamma and X rays for babies, children, teens, young adults, pregnant females, old people and sick people ? How can the art of medicine best use low dose irradiation ? Is ionizing radiation essential for optimal physiologic functions ? For life ? Should whole populations be supplemented ? How ? Should control be with health physics professionals, the medical profession, public health officials, or politicians?

 

 

8. References

 

Abbatt, J.D., Hamilton, T.R. and Weeks, J.L. (1983) Epidemiological studies in three corporations covering the nuclear fuel cycle. Biological Effects of Low-Level Radiation, Proc.IAEA-STI/Pub/646, International Atomic Energy Agency, Vienna, 351-361.

Bogoljubov, W.M. (1988) Clinical aspects of radon therapy in the U.S. S. R. Z. Phys. Med. Balneol. Med. Klimatol. 17,59-61.

Cohen, B.L.(1993) Test of the linear-no threshold theory of radiation carcinogenesis, ICSE Conference, Paris.

Darby, S.C., Kendall, G.M., Fell, T.P. et al.(1988) A summary of mortality and incidence of cancer in men from the United Kingdom who participated in the United Kingdom atmospheric weapons tests and experimental programs, Br. Med. J. 296, 332-340.

Gilbert, E.S., Fry, S.A., Wiggs, L.D. et al. 1989) Analysis of combined mortality data on workers at the Hanfort Site, Oak Ridge National Laboratory, and Rocky Flats Nuclear Weapons Plant, Radiat. Res. 120, 19.

Gribbin, M.A., Weeks, J.L., and Howe, G.R.(1993) Cancer mortality (1956-1985) among male employees of Atomic Energy Limited with respect to occupational exposure to low-linear-energy-transfert ionizing radiation, Radiat Res 3, 375.

Haynes, R.M.(1988) The distribution of domestic radon concentrations and lung cancer mortality in England and Wales, Rad. Prot. Dosim. 93-4.

Kendall, G.M., Muirhead, C.R., MacGibbon, B.H. et al. (1992) Mortality and ocupational exposure to radiation ; first analysis of the National Registry for Radiation Workers, Brit Med J ,304, 220.

Luckey, T.D.(1959) Antibiotics in Nutrition, in H.S.Goldberg (ed), Antibiotics, Their Chemistry and Non-Medical Uses, D. Van Nostrand Publisher, Princeton, pp174-321.

Luckey, T.D. (1990) Hormesis with Ionizing Radiation, CRC Press, Boca Raton Publisher, In Japanese Soft Science Inc., Tokyo.

Luckey, T.D. (1993) Radiation Hormesis. CRC Press, Boca Raton Publisher, 1991. In Japanese, Soft Science, Inc., Tokyo.

Luckey, T.D., Gordon, H.A., Wagner, M. and Reyniers, J.A. (1956) Growth of germfree birds fed antibiotics, Antibiot. Chemother. 6, 36-40.

Matanoski, G.M. (1985) Health Effects of Low Level Radiation in Shipyard workers, DOE Final Report. E.1.99 DOE/EV/10095-T 1 and 2. DOE, Washington.

Moore, P.R., Evenson, A., Luckey, T.D., McCoy, E., Elvehjem, C.A. and Hart, E.B. (1946) The use of sulfasuxadine, streptothrycin and streptomycin in nutritional studies with the chick, J. Biol. Chem. 165, 437-441.

Nageli, U. (1893) Ueber oligodynamische Erscheinungen in Lebenden Zellen. Gesellsch, f.b. Naturwissenschaft 33, 1-4.

Raman, E., Dulberg, C.S. and Spasoff, R.A. ( 1987) Mortality among Canadian military personel exposed to low-dose radiation, Can. Med. Assoc. J. 136, 1951-55.

Richet, C. (1906) De l'action de doses minuscules de substance sur la Fermentation Lactique - troisième mémoire - Périodes d'accélération et de ralentissement, Arch. Intern. Physiologie 4, 18-50.

Robinette, C.D., Jablon, S. and Preston, T.L. (1985) Studies of Participants in Nuclear Tests, National Research Council Final Report. DOE/EVO1577, Washington.

Shimizu, Y., Kato, H., Schull, W.J. and Mabuchi, K. (1992) Dose response analysis among atomic-bomb survivors exposed to low-level radiation, in T. Sugahara, L. Sagan and T. Aoyama (eds.) Low Dose Irradiation and Biological Defense Mechanisms, Exerpta Medica Publisher, Amsterdam, pp. 71-74.

Southam, C.M. and Ehrlich, J. (1943) Effects of extract of western red-ceder heartwood on certain wood decaying fungi in culture, Phytopathol. 33, 517-524.

Sugahara, T., Sagan, L.A. and Aoyama, T.(1992) Low Dose Irradiation and Biological Defense Mechanisms, Excerpta Medica Publisher, Amsterdam.

Yamada, S., Nemoto, K., Ogawa, Y., Yakatou, Y., Hosi, A. and Sakamoto; K.(1992) Anti-tumor effect of low dose total (or half) body irradiation and changes of the functional subset of peripheral blood lymphocytes in nonHodgkin's lymphoma patients after TBI (HBI),in T. Sugahara, L. Sagan and T. Aoyama (eds.) Low Dose Irradiation and Biological Defense Mechanisms, Exerpta Medica Publisher, Amsterdam, pp. 113-116.

 

 

 

 



* Plenary lecture presented at the 7th GIRI Meeting, November 1993, Montpellier, France.