Extensive Evidence Suggesting Hormesis

1. Experimental Evidence

1.1. Cancer Prevention

Bhattarcharjee 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 Rate

In 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 studies

1-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.
2-Mifune (1992) (Mifune et al. 1992) and his co-workers indicated that in a spa area (Misasa), with an average indoor radon level of 35 Bq/m3, the lung cancer incidence was about 50% of that in a low-level radon region. Their results also showed that in the above mentioned high background radiation area, the mortality rate caused by all types of cancer was 37% lower.
3-According to Mine et al. (1981), among A-bomb survivors from Nagasaki, in some age categories, the observed annual rate of death is less than what is statistically expected.
4-Kumatori and his colleagues (Kumatori et al. 1980) reported that according to their 25 year follow up study of Japanese fishermen who were heavily contaminated by plutunium (hydrogen bomb test at Bikini), no one died from cancer.

2.2. Background Radiation Studies

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).
2-In a very large scale study in U.S.A, it was found that the mortality rate due to all malignancies was lower in states with higher annual radiation dose (Frigerio 1976).
3- In a large scale Chinese study, it was showed that the mortality rate due to cancer was lower in an area with a relatively high background radiation (74,000 people), while the control group (78,000 people) who lived in anarea with low background radiation had a higher rate of mortality (Wei L 1990).
4-In the U.S.A., it was indicated that significantly, the total cancer mortalityis inversely correlated with background radiation dose (Cohen BL. 1993).

2.3. Nuclear Power Plant studies

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).
2-In U.K also it was indicated that cancer frequency among nuclear powerplant workers was lower than the national average (Kendal et al. 1992).

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)
According to this theory, low doses of ionizing radiation induce the production of special proteins, that are involved in DNA repair processes (Ikushima 1996). Studies using two dimensional gel electrophoresis indicated new proteins in cells irradiated with low doses of radiation. Also, it was further shown that cycloheximide, a protein synthesis inhibitor blocks this hormetic effect. The function and importance of these radiation induced proteins is still unknown. Also it was foud that inhibitors of poly ADP-ribose polymerase, an enzyme implicated in DNA strand break rejoining could prevent the induction of adaptive response (for a review see Wolff 1998).

2-Free radical detoxification (Molecular level)
In 1987 Feinendengen and his co-workers indicated that low doses of ionizing radiation cause a temporary inhibition in DNA synthesis (the maximum inhibitionat 5 hours after irradiation). This temporary inhibition of DNA synthesis would provide a longer time for irradiated cells to recover (Feinendengen et al. 1987). This inhibition also may induce the production of free radical scavengers, so irradiated cells would be more resistant to any further exposures.

3-Stimulation of immune system (Cellular level)
Despite the fact that high doses of ionizing radiation are immunosupressive, many studies have indicated that low doses radiation may stimulate the function of the immune system. In 1909 Russ first showed that mice treated with low-level radiation were more resistant against bacterial disease (Russ VK 1909).Later in 1982 Luckey published a large collection of references supporting immunostimulatory effects of low doses of ionizing radiation (Luckey TD 1982).