Radiation HormesisHormesis at a Glance All living organisms evolved and exist in a sea of ionizing radiation, much of which is internal. It is a general belief that low doses of ionizing radiation produce detrimental effects proportional to the effects produced by high-level radiation. Over the past decades, however, some pioneer scientists reported that low-dose ionizing radiation is not only a harmless agent but often has a beneficial or hormetic effect. That is, low-level ionizing radiation may be an essential trace energy for life, analogous to essential trace elements. It has been even suggested that about one third of all cancer deaths are preventable by increasing our low dose radiation. Introduction Despite the fact that high doses of ionizing radiation are detrimental, substantial data from both humans and experimental animals show that biologic functions are stimulated by low dose radiation (Luckey 1980). The word "hormesis" is derived from the Greek word "hormaein" which means "to excite". It has long been known that many popular substances such as alcohol and caffeine have mild stimulating effects in low doses but are detrimental or even lethal in high doses. In the early 1940s C. Southam and his coworker J. Erlish found that despite the fact that high concentrations of Oak bark extract inhibited fungi growth, low doses of this agent stimulated fungi growth. They modified starling's word "hormone to "hormesis" to describe stimulation induced by low doses of agents which are harmful or even lethal at high doses. They published their findings regarding the new term "hormesis" in 1943 (Bruce M. 1987). Generally, hormesis is any stimulatory or beneficial effect, induced by low doses of an agent, that can not be predicted by the extrapolation of detrimental or lethal effects induced by high doses of the same agent. Hormesis and LNT Model In the early days of X-rays and radioactivity it was generally believed that ionizing radiation has numerous beneficial effects. It was claimed that blindness might be cured by X-rays. Ladies corsets contained radium! Drinking mineral water containing radium was very popular. People went to spas to drink radioactive water or stayed for hours in caves to be irradiated by ionizing radiation (for a review see Wolff 1992). Between 1925 and 1930 over 400,000 bottles of distilled water containing radium 226 and radium 228 were sold. It was advertised that some mixtures could treat over 150 disease, especially lassitude and sexually impotence (Macklis 1990). It is estimated that the collective skeletal radiation dose of victims of such radioactive medicine may had exceeded 350 Sv by the time the user died (Macklis 1991). Gradually people found that the improper use of ionizing radiation could lead to many complications and harmful effects. Later, In 1927 Herman J. Muller,a Nobel Prize winner, found that X-rays are mutagen and there is a linear relationship between mutation rate and dose. He proposed that mutations, which are induced by radiation (or other mutagens) are mostly detrimental. When it was generally accepted that excessive radiation may be harmful, the first regulations for dose limits were introduced. . Despite carcinogenicity of X-rays was observed as early as 1902 (Kathren 1996), the first radiation protection limits suggested in 1925 and for three decades these limits were based on the concept of a tolerance dose (Muller 1928). Surprisingly, until the end of World War II, ionizing radiation was considered agreat scientific miracle. After the war the development of nuclear weapons and later increased use of nuclear power changed this great miracle into radiophobia. At that time people became afraid of even very small doses of ionizing radiation. Extensive Evidence Suggesting Hormesis 1. Experimental Evidence 1.1. Cancer PreventionBhattarcharjee in 1996 showed that when the mice preirradiated with just adapting doses of 1 cGy/day for 5 days (without a challenge dose), thymic lymphoma was induced in 16% of the animals (Bhattarcharjee 1996). Interstingly, when preirradiated mice were exposed to a 2 Gy challenge dose, thymic lymphoma was induced again in 16% of the animals. However, the challenge dose alone, induced thymic lymphoma in 46% of the mice. From these results, it can be concluded that the low dose preirradiation possibly cancel the induction of thymic lymphoma by the 2 Gy challenge dose. In 1996, Azzam and his colleagues showed that a single exposure of C3H 10T1/2 cells to doses as low as 0.1 cGy reduces the risk of neoplastic transformations. They suggested that a single low-dose at background or occupational exposurelevels, may reduce cancer risk. Recently, Redpath and his co-workers haveconfirmed the findings of Azzam and his coworkers (Azzam et al. 1996). To test the generality of the observations of Azzam and his colleagues, they used the Hela x skin fibroblast human hybrid cell. Using a similar experimental protocol, they demonstrated a significantly reduced transformation frequency for adapted to unirradiated cells (pooled data from four separate experiments).In addition, recently Mitchel and his co-workers in Canada have indicated that a low dose preirradiation (10 cGy, 0.5 Gy/h) modifies latency for radiation induced myeloid leukemia in CBA/H mice after exposure to a 1 Gy chronic radiation exposure (Mitchel et al. 1999). They showed that the latent period for development of acute myeloid leukemia (AML) was significantly increased by the prior low radiation dose. Interestingly, according to T.D. Luckey one third of all cancer deaths are premature and preventable by low-level ionizing radiation (Luckey 1994, 1997). 1.2. Survival RateIn 1996, Yonezawa and his colleagues indicated that when 21-ICR mice were exposed to a 8 Gy of X-rays, about 30% of the animals survived 30 days after the irradiation. However, when mice preirradiated with 5 cGy of X-rays, the survival rate increased to about 70% (Yonezawa et al. 1996). 2. Epidemiological Evidence Although radiation hormesis data are still incomplete, extensive epidemiological studies have indicated that radiation hormesis is really exist. A briefreview on this irrefutable evidence is as follows: 2.1. Japanese studies1-According to UNSCEAR report (1994), among A-bomb survivors from Hiroshimaand Nagazaki who received doses lower than 200 mSv, there was no increase in the number of total cancer death. Mortality caused by leukemia was evenlower in this population at doses below 100 mSv than age-matched controlcohorts. 1-In an Indian study, it was observed that in areas with a high-background radiation level, the incidence of cancer and also the mortality rate due to cancer was significantly less than similar areas with a low backgroundradiation level (Nambi and Soman 1987). 1-In a Canadian survey the mortality caused by cancer at nuclear power plants was 58% lower than the national average (Abbat et al. 1983). The Mechanism of Hormetic Phenomena Although still we do not know the entire mechanisms of radiation hormesis, the following theories may explain this process: 1-DNA repair (Mollecular level) 2-Free radical detoxification (Molecular level) 3-Stimulation of immune system (Cellular level) Conclusion Our radiation protection policy is based on linear extrapolation from the dose-response data of high doses of ionizing radiation. According to the results of many worldwide studies, this assumption is not compatible with observed health effects of low levels of radiation. Obviously LNT and current radiation protection regulations exaggerate the risk of low level ionizing radiation (in the range of 1-50 cGy) and cause radiophobia (Yalow RS 1990). It is concluded that according to new findings, the existence of radiation hormesis and adaptive response are not deniable and abandoning the LNT theory in low dose risk estimations will be a real nessecity in the near future. |