Inflammation from Radiation

Also see:
Radiation Increases Breast Cancer Incidence
Harm of Prenatal Exposure to Radiation
Caffeine and Skin Protection
Topical Vitamin E and ultraviolet radiation on human skin
Preventing Breast Cancer
We Are Giving Ourselves Cancer
Alice Stewart: The woman who knew too much
Breast Cancer
Radiation and Growth – Ray Peat
Bone Density: First Do No Harm

“MRI (magnetic resonance imaging) and ultrasound imaging are much safer than x-rays and can provide better images of tissues, and can also provide detailed information about tissue functions and metabolism.

The excitation of electrons in the tissues by radiation has catalytic effects tbat produce long-lasting changes in biological functions that are more important than any immediate genetic mutations.” -Ray Peat, PhD

Int J Radiat Oncol Biol Phys. 1990 Dec;19(6):1425-9.
Delayed appearance of lethal and specific gene mutations in irradiated mammalian cells.
Little JB, Gorgojo L, Vetrovs H.
We have examined the occurrence of lethal and 6-thioguanine resistant (hprt locus) mutants among the progeny of irradiated CHO and BALB/3T3 cells. The expression of lethal mutations, as measured by a reduced cloning efficiency in the progeny cell population, was detected up to 30 mean population doublings after x-radiation. Preliminary evidence indicates that the expression of mutations at the hprt locus may also be delayed for at least 6-7 population doublings. These results suggest that radiation can induce genetic instability in cells, resulting in an increased rate of spontaneous mutations which persists for many generations of cell division. These findings are discussed in terms of their possible influence on the response of irradiated tumor cell populations in vivo.

Int J Radiat Biol. 2003 Feb;79(2):129-36.
Radiation dose-dependent increases in inflammatory response markers in A-bomb survivors.
Hayashi T, Kusunoki Y, Hakoda M, Morishita Y, Kubo Y, Maki M, Kasagi F, Kodama K, Macphee DG, Kyoizumi S.
PURPOSE:
The well-documented increases in malignant tumours in the A-bomb survivors have recently been supplemented by reports that non-cancer diseases, including cardiovascular disease, may also have increased in incidence with increasing radiation dose. Given that low-level inflammatory responses are widely accepted as a significant risk factor for such diseases, we undertook a detailed investigation of the long-term effects of ionizing radiation on the levels of the inflammatory markers C-reactive protein (CRP) and interleukin 6 (IL-6) in A-bomb survivors.
MATERIALS AND METHODS:
Blood samples were taken from 453 participants in a long-term epidemiological cohort of A-bomb survivors. Plasma levels of CRP and IL-6 were measured using standard antibody-mediated procedures. Relationships between CRP or IL-6 levels and radiation dose were then investigated by multivariate regression analysis. Blood lymphocytes from each individual were used for immunophenotyping by flow cytometry with murine monoclonal antibodies to CD3, CD4 and CD8.
RESULTS:
CRP levels were significantly increased by about 31% Gy(-1) of estimated A-bomb radiation (p=0.0001). Higher CRP levels also correlated with age, male gender, body mass index and a history of myocardial infarction. After adjustments for these factors, CRP levels still appeared to have increased significantly with increasing radiation dose (about 28% increase at 1Gy, p=0.0002). IL-6 levels also appeared to have increased with radiation dose by 9.3% at 1Gy (p=0.0003) and after multiple adjustments by 9.8% at 1Gy (p=0.0007). The elevated CRP and IL-6 levels were associated with decreases in the percentages of CD4(+) helper T-cells in peripheral blood lymphocyte populations.
CONCLUSIONS:
Our results appear to indicate that exposure to A-bomb radiation has caused significant increases in inflammatory activity that are still demonstrable in the blood of A-bomb survivors and which may lead to increased risks of cardiovascular disease and other non-cancer diseases.

Int J Radiat Biol. 2003 Oct;79(10):777-85.
IL-1beta, TNFalpha and IL-6 induction in the rat brain after partial-body irradiation: role of vagal afferents.
Marquette C, Linard C, Galonnier M, Van Uye A, Mathieu J, Gourmelon P, Clarençon D.
PURPOSE:
To evaluate the central nervous system neuroimmune and inflammatory responses during the prodromal phase of the acute irradiation syndrome in rat brains after partial-body exposure (head-protected) and to investigate the potential neural signalling pathways from the irradiated periphery to the non-irradiated brain.
MATERIAL AND METHODS:
The study included four groups of rats: one irradiated group and one sham irradiated group, each containing non-vagotomized and vagotomized rats. In vagotomized rat groups, the subdiaphragmatic vagal section surgery was carried out 45 days before the irradiation exposure. The rats were partial-body irradiated with the head shielded with (60)Co gamma-rays to a dose of 15 Gy. They were sacrificed 6 h after the end of exposure. The hypothalamus, hippocampus, thalamus and cortex were then collected, and the concentrations of IL-1beta, TNFalpha and IL-6 in each were measured by ELISA assays.
RESULTS:
Six hours after irradiation, IL-1beta levels had increased in the hypothalamus, thalamus and hippocampus, and TNFalpha and IL-6 levels had increased significantly in the hypothalamus. Vagotomy before irradiation prevented these responses.
CONCLUSIONS:
It was concluded that the hypothalamus, hippocampus, thalamus and cortex react rapidly to peripheral irradiation by releasing pro-inflammatory mediators. The results also show that the vagus nerve is one of the major ascending pathways for rapid signalling to the brain with respect to partial body irradiation.

Rinsho Byori. 1994 Apr;42(4):313-9.
[Health effects of atomic bomb radiation].
[Article in Japanese]
Shigematsu I.
The health effects of atomic bomb radiation have been studied by the Atomic Bomb Casualty Commission (ABCC) and its successor, the Radiation Effects Research Foundation (RERF) based on a fixed population of atomic bomb survivors in Hiroshima and Nagasaki which had been established in 1950. The results obtained to the present can be classified into the following three categories: (1) The effects for which a strong association with atomic bomb radiation has been found include malignant neoplasms, cataracts, chromosomal aberrations, small head size and mental retardation among the in utero exposed. (2) A weak association has been found in the several sites of cancers, some non-cancer mortalities and immunological abnormalities. (3) No association has been observed in some types of leukemia, osteosarcoma, accelerated aging, sterility and hereditary effects.

“When a dose of radiation similar to a diagnostic x-ray is given to cells in culture, they are still emitting induced light after an hour or more (Vicker, et al., 1991). The genetic mutations produced by radiation are still occurring hours or days after the exposure; the observations in the Japanese suggest that they might keep occurring years after the exposure.” -Ray Peat, PhD

Radiat Res. 1991 Dec;128(3):251-7.
Ionizing radiation at low doses induces inflammatory reactions in human blood.
Vicker MG, Bultmann H, Glade U, Häfker T.
Irradiation of whole blood with 137Cs gamma rays intensifies the oxidative burst. Oxidant production was used as an indicator of inflammatory cell reactions and was measured by luminol-amplified chemiluminescence after treatment with inflammatory activators including bacteria, the neutrophil taxin formyl-Met-Leu-Phe, the Ca2+ ionophore A23187, the detergent saponin, and the tumor promoter phorbol ester. The irradiation response is dose-dependent up to about 100 microGy, is detectable within minutes, persists at least 1 h, and is transmitted intercellularly by a soluble mediator. The response is completely inhibited by Ca2+ sequestration in the presence of A23187 or by adenosine, indicating its Ca2+ dependency, and by the phospholipase A2 blocker p-bromphenacyl bromide. However, inhibition by the cyclooxygenase blocker aspirin is sporadic or absent. Blood taken after diagnostic examination of lungs with X rays also exhibited intensified chemiluminescence. These reactions implicate a role for specific amplifying mediator pathways, especially metabolites of the arachidonic acid cascade, in the response: “damage and repair” to cells or DNA plays little or no role. Our results provide evidence for a new mechanism of radiation action with possible consequences for the homeostasis of reactions involving inflammation and second messengers in human health and early development.

“People talk about DNA being altered when it is “hit” by radiation, and everyone who has taken a biology course has probably heard that the ”target size” of a gene or a virus determines the likelihood that it will be damaged by a given dose of radiation. That quaint relic of primitive radiation biophysics is useful for nuclear power corporations, and for dentists, and for anyone who wants to sell whole body scans to the public. But that dogma has now been very firmly knocked out by hundreds of direct hits by experimental data, that show that irradiated cells transmit something to other cells that weren’t exposed to the radiation, in a “radiation bystander effect.”” -Ray Peat, PhD

Hum Exp Toxicol. 2004 Feb;23(2):91-4.
Commentary on radiation-induced bystander effects.
Wright EG.
The paradigm of genetic alterations being restricted to direct DNA damage after exposure to ionizing radiation has been challenged by observations in which effects of ionizing radiation arise in cells that in themselves receive no radiation exposure. These effects are demonstrated in cells that are the descendants of irradiated cells (radiation-induced genomic instability) or in cells that are in contact with irradiated cells or receive certain signals from irradiated cells (radiation-induced bystander effects). Bystander signals may be transmitted either by direct intercellular communication through gap junctions, or by diffusible factors, such as cytokines released from irradiated cells. In both phenomena, the untargeted effects of ionizing radiation appear to be associated with free radical-mediated processes. There is evidence that radiation-induced genomic instability may be a consequence of, and in some cell systems may also produce, bystander interactions involving intercellular signalling, production of cytokines and free radical generation. These processes are also features of inflammatory responses that are known to have the potential for both bystander-mediated and persisting damage as well as for conferring a predisposition to malignancy. Thus, radiation-induced genomic instability and untargeted bystander effects may reflect interrelated aspects of inflammatory type responses to radiation-induced stress and injury and contribute to the variety of the pathological consequences of radiation exposures.

“Cortisol is protective against the acute inflammatory effects of radiation (Beetz, et al., 1997), but progesterone has those effects without the handful effects of excess cortisol.” -Ray Peat, PhD
.
Int J Radiat Biol. 1997 Jul;72(1):33-43.
Induction of interleukin 6 by ionizing radiation in a human epithelial cell line: control by corticosteroids.
Beetz A, Messer G, Oppel T, van Beuningen D, Peter RU, Kind P.
The cutaneous radiation syndrome after therapeutic or accidental exposure of human skin to ionizing radiation (IR) is accompanied by inflammatory processes which are controlled partly by proinflammatory cytokines. Besides tumour necrosis factor (TNF)-alpha and interleukin (IL)1, the pluripotent cytokine IL-6 belongs to the key mediators of inflammation. So far, there are no reports about the regulation of IL-6 by IR in epidermal cells. As an in vitro model to study the effects of IR on IL-6 gene expression, we treated the human epithelial HeLa cell line with different single X-ray doses between 1 and 20 Gy. Twenty-four hours after irradiation the IL-6 secretion was dose-dependently enhanced as measured by ELISA. At the transcriptional level, a slight increase of IL-6 transcripts was already detectable 1 h after irradiation, with maximum levels at 2 h, and a decline to baseline levels between 8 and 24 h. Addition of the transcriptional inhibitor actinomycin D inhibited the inducibility of IL-6 mRNA by TPA and IR. As the IL-6 promoter contains multiple binding sites for activated glucocorticoid receptors within the 5′ regulatory region, the potential modulation of IL-6 expression by the corticosteroids hydrocortisone, dexamethasone and mometasone furoate was included in our study to modify the radiation-induced stress response. All corticosteroids applied could efficiently downregulate TPA- or radiation-induced IL-6 expression on both gene expression and protein levels. Mometasone furoate, followed by dexamethasone, was found to be most effective at low concentrations (1 nM), whereas hydrocortisone had to be applied at about 100-fold higher concentrations to achieve comparable inhibition. This experimental model is aimed at understanding the molecular circuits following IR, and thus to provide a basis for the treatment of radiation effects in skin.

Radiat Res. 1994 Jan;137(1):89-95.
Autoantibodies and immunoglobulins among atomic bomb survivors.
Fujiwara S, Carter RL, Akiyama M, Akahoshi M, Kodama K, Shimaoka K, Yamakido M.
The purpose of this study was to determine if exposure to atomic bomb radiation affects immune responsiveness, such as the occurrence of autoantibodies and levels of immunoglobulins. Rheumatoid factor, antinuclear antibody, antithyroglobulin antibody, anti-thyroid-microsomal antibody and immunoglobulin levels (IgG, IgM, IgA and IgE) were measured among 2,061 individuals exposed to atomic bomb radiation in Hiroshima and Nagasaki whose estimated doses ranged from 0 to 5.6 Gy. The prevalence and titers of rheumatoid factor were found to be increased in the individuals exposed to higher radiation doses. The IgA level in females and the IgM level in both sexes increased as radiation dose increased, although the effects of radiation exposure were not large. No effect of radiation was found on the prevalence of antinuclear antibody, antithyroglobulin antibody and anti-thyroid-microsomal antibody or on the levels of IgG and IgE.

JAMA. 2006 Mar 1;295(9):1011-22.
Radiation dose-response relationships for thyroid nodules and autoimmune thyroid diseases in Hiroshima and Nagasaki atomic bomb survivors 55-58 years after radiation exposure.
Imaizumi M, Usa T, Tominaga T, Neriishi K, Akahoshi M, Nakashima E, Ashizawa K, Hida A, Soda M, Fujiwara S, Yamada M, Ejima E, Yokoyama N, Okubo M, Sugino K, Suzuki G, Maeda R, Nagataki S, Eguchi K.
CONTEXT:
Effects of irradiation on thyroid diseases such as thyroid nodules and autoimmune thyroid diseases have not been evaluated among people exposed to radiation more than 50 years in the past.
OBJECTIVE:
To evaluate the prevalence of thyroid diseases and their radiation-dose responses in atomic bomb survivors.
DESIGN, SETTING, AND PARTICIPANTS:
Survey study comprising 4091 cohort members (mean age, 70 [SD, 9] years; 1352 men and 2739 women) who participated in the thyroid study at the Radiation Effects Research Foundation. Thyroid examinations were conducted between March 2000 and February 2003.
MAIN OUTCOME MEASURES:
Prevalence of thyroid diseases, including thyroid nodules (malignant and benign) and autoimmune thyroid diseases, and the dose-response relationship of atomic bomb radiation in each thyroid disease.
RESULTS:
Thyroid diseases were identified in 1833 (44.8%) of the total participants (436 men [32.2% of men] and 1397 women [51.0% of women]) (P<.001). In 3185 participants, excluding persons exposed in utero, not in the city at the time of the atomic bombings, or with unknown radiation dose, the prevalence of all solid nodules, malignant tumors, benign nodules, and cysts was 14.6%, 2.2%, 4.9%, and 7.7%, respectively. The prevalence of positive thyroid antibodies, antithyroid antibody-positive hypothyroidism, and Graves disease was 28.2%, 3.2%, and 1.2%, respectively. A significant linear dose-response relationship was observed for the prevalence of all solid nodules, malignant tumors, benign nodules, and cysts (P<.001). We estimate that about 28% of all solid nodules, 37% of malignant tumors, 31% of benign nodules, and 25% of cysts are associated with radiation exposure at a mean and median thyroid radiation dose of 0.449 Sv and 0.087 Sv, respectively. No significant dose-response relationship was observed for positive antithyroid antibodies (P = .20), antithyroid antibody-positive hypothyroidism (P = .92), or Graves disease (P = .10).
CONCLUSIONS:
A significant linear radiation dose response for thyroid nodules, including malignant tumors and benign nodules, exists in atomic bomb survivors. However, there is no significant dose response for autoimmune thyroid diseases.