Professor and Chairman Emeritus of the Dept. of Biochemistry of the U. Missouri-Columbia Medical School, Dr. T. D. Luckey, reports (1991) on radiation hormesis in immunity: 'Irradiation of pregnant animals-and the foetuses in utero caused an astonishing decrease of the mortality of the infected baby mice'. (Mayr and Paulas 1989) In 1896 Shrader contradicted J.J. Thompson's claim that the new X-ray was not bactericidal by infecting guinea pigs with diphtheria bacillus. Those previously exposed to X-rays survived, while the controls died within 24 hr. Decreased susceptibility to infection and decreased midlife cancer explained the increased mean lifespan low doses. Decreased infection and cancer relate to improved immune competence, confirmed by evidence of increased humoral and cell-mediated immune competence following low doses. Increased cell repair enzymes and enhanced immune competence are keys to understanding many physiologic effects of low doses. DNA repair enzymes are effective for exposures which are low enough to provide adequate time to repair the DNA. Also important are repair of cell membranes, altered enzyme concentrations, and changed metabolic priorities. The interaction of immune system functions are absent in radiation experiments with cells in culture. Thymic hormones contribute to lymphocyte maturation and differentiation. The radiation syndrome in guinea pigs was greatly improved by injection of thymic hormone preparations. The spleen is vital to immunity. Exposure of mice activated splenic cell proliferation.Whole-body exposures increased spleen follicle development and spleen plaque-forming cells in mice, two criteria of an active immune system. DNA synthesis of spleen cells was also stimulated. Low doses increased the mitogenic responsiveness of mouse spleen cells as well as mitogen induced proliferation and function in both animal and human T cells. Stimulation of spleen function appears to be the basis for recent clinical application of whole-body exposures of cancer patients to 10 cGy once or twice weekly. The activation of immune reactions correlates with tumor regression in some patients.

Dr. Luckey also reports (1991) on wound healing: A simple, direct measure of the effect of low doses on physiologic repair is wound healing following incision of skin. Pretreatment with low doses of radiation causes accelerated healing when compared with either unexposed controls or animals exposed following the incision. Increased numbers of circulating lymphocytes were routinely found following low doses of whole body radiation. Repeated local exposures of about 1 Gy of X-rays were used to treat patients with problems, such as acute inflammation. This became a much discussed issue for two decades. Interest in this phenomenon stopped in 1942 with the availability of antibiotics and the infusion of money to study the harmful effects of excess exposure to ionizing radiation.

Dr. Luckey reports on the effects of radiation on the morbidity and mortality of animals: In 1908 Gerhartz found increased survival in irradiated rabbits injected with diphtheria toxin. Increased resistance to bacterial toxins was exhibited by irradiated animals. Radiation-enhanced resistance to infection was found in rodents and invertebrates. Survival was significantly longer in immunized mice infected with Proteus milabilis following a single exposure to 4.5 Gy X-rays. Irradiation of guinea pigs exposed to pneumonia induced decreased congestion and abscess formation, prevented development of the disease, or caused the disease to recede more rapidly. The intensity and duration of disease in cholera-infected guinea pigs was decreased by 1 Gy exposure to X-rays. Rabbits exposed to 3.5 Gy of X-rays either 12 h before or 5 h following intravenous injection with streptococci survived longer. Wounds from subcutaneous injection of staphylococci healed faster in irradiated rabbits. When exposed to 0.7 to 2 Gy of X-rays following exposure to lethal doses of pneumococci, some dogs recovered. Sheep exposed to 2 to 3 Gy of X-rays following lethal injection with clostridia had lower mortality. Experimental viral infections in rabbits, mice, and cats were reduced by repeated exposure to X-rays. Mice exposed to 3 Gy of X-ray survived longer when infected with a lymphocytic virus. Irradiation of fetuses in utero caused a 50% decrease in the mortality rate of the infected baby mice. Mice exposed to 150 cGy total body irradiation at 5 and 12 days following infection with friend virus recovered while controls died within 40 d. Accidental infection of one human was treated with X-ray.

In the conference summary for the November 1996 BELLE Conference, Dr. K. Sugahara reports (1996) that: "In radiation protection, direct induction of cancer-related mutations by radiation has been assumed. Somatic cell mutation frequency dose-response in erythrocytes of A-bomb survivors showed that the doubling dose is about 1.20Sv. Their conclusion is that this observation is in line with the hypothesis that radiation-induced somatic cell mutations are the major cause of excess cancer risk after radiation exposure. Mutation and transformation were different to each other in response pattern to radiation. These studies may support a different mechanism for radiation-carcinogenesis from the above hypothesis."

From the abstract, Dr. E.I. Azzam and colleagues report (1996) that: "A single exposure of quiescent C3H 10T1/2 cells to a dose of 0.1, 1.0 or 10 cGy followed by a 24-h incubation reduced the risk of neoplastic transformation from the spontaneous level to a rate three- to four-fold below that level. If similar processes are induced in human cells, a single low dose at background or occupational exposure levels may reduce rather than increase cancer risk, a conclusion inconsistent with the linear no-threshold model of cancer risk from radiation."

In the conference summary for the BELLE Conference, Nov. 1996, Drs. J. Smith-Sonneborn and Barbee, report: "The global molecular response to stress includes a dramatic change in gene expression and elevated synthesis of heat shock or other stress-induced protective proteins. Stressors include heat, heavy metals, oxidants, bacterial and viral infection, and most recently, exercise. Oxidant damage and/or heat are major components in the induction of the adaptive protective response. Radiation induces members of the heat shock family and the coordinated expression of antioxidant defenses. The model system Paramecium was used to assess mechanisms involved in the beneficial effects of low doses of otherwise harmful agents; e.g. radiation induced increased longevity and peroxide induction of oxidative tolerance."

From an abstract, Dr. Alexander Kuzin, Corresponding Member of the Academy of Sciences of Russia, Honorary Doctor of the Leeds University (England), State Prize Winner of the USSR (1987), Head of the Group of Radiational Biochemistry and Cellular Regulation, of the Institute of Biophysics, reports (1993) that: The different cellular responses to high (suppressive) and low (stimulant) doses of atomic radiation suggest understanding of radiation hormesis, since the well developed mechanisms of damaging effect of atomic radiation (radiodamage of DNA, chromosomal aberrations, death of radiosensitive cells) cannot explain the converse effects of low stimulant radiation doses. Here the direct or indirect excitation of membrane receptors comes to the foreground. The excitation activates membrane-bound enzymes which control many vitally important processes.

Drs. Kiyohiko Sakamoto and Miyake Miyamoto of the Tohoku University School of Medicine, and Nobuyuki Watabe of the Tohoku Teishin Hospital report further (1987) on TBI effects on mice tumors: "Total body irradiation (TBI) is considered to bring about an immuno-suppressive effect on an organism, on the basis of data obtained from sublethal doses of TBI. In experimental studies, an increase in the number of cells required for a tumor incidence of 50% in mice exposed to 10 rad showed a remarkable increase 6 hours to 15 hours after irradiation. TBI of 10 rad also showed an enhancement effect on tumor cell killing when given 12 hours before local tumor irradiation. Immunological studies suggested that 10 rad of TBI caused increasing tumor immunity in irradiated mice. Clinical trials... are now being undertaken on the basis of these experimental data, and the effect of TBI on tumor control appears promising."

Drs. M. Miyamoto and K. Sakamoto of Tohoku University School of Medicine report on TBI effects on mice tumors (1987) that: "(T)otal body irradiation (TBI) on non-tumor bearing and tumor bearing mice of 0.1 Gy during 6-12 hours before tumor cell inoculation demonstrated a need for a larger number of tumor cells (approximately 2.5 times) for 50 per cent tumor incidence, compared to mice that did not receive TBI. In tumor bearing mice given 0.1 Gy of TBI only, tumor cell killing effect was not detected, however enhancement of tumor cell killing effect and prolonged growth delay were observed when tumor bearing mice were treated with 0.1 Gy of TBI combined with local irradiation on tumors, especially cell killing effect was remarkable in dose range over 6 Gy of local exposure. The mechanism of the effect of 0.1 Gy TBI is considered to be host mediated reactions from our other experimental results."