A Nontarget Mechanism to Explain Carcinogenesis Following α-Irradiation (original) (raw)
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Role of Low-Level Ionizing Radiation in Multi-Step Carcinogenic Process
Health Physics, 1996
In view of our current understanding of experimental in vitro and in vivo studies, as well as of the epidemiological data, carcinogenesis is the result of many endogenous and exogenous factors. No single factor "causes" cancer. A number of extant theories of carcinogenesis and of ionizing radiation's role in the process have been reviewed. An integration of the stem cell theory, the theory of "oncogeny as partially blocked ontogeny," the initiatiodpromotiodprogression model of carcinogenesis, the oncogeneltumor suppressor gene theory, and mutatiodepigenetic theories of carcinogenesis was attempted by linking all of them with the process of intercellular communication. This integration was done by examining how extra-, intra-and inter-cellular communication might be affected by the current known facts of the types of radiationinduced biological effects, such as gene and chromosomal mutations, cell killing, including apoptosis and epigenetic alterations of gene expression. Finally, an examination of the possible role of low-level radiation in the multi-step carcinogenetic process, which might have given rise to the excess cancers attributable to radiation exposure in the survivors of the atomic bombs, was attempted.
Hallmarks of radiation carcinogenesis: ignored concepts
International Congress Series, 2003
The research challenge in radiobiology is to determine the biological and health effects of low-level acute and chronic low-level ionizing radiation effects. The public's perception is that ''any'' radiation is ultimately going to ''cause'' bad health effects. Clearly, the scientific view is that any demonstrated health effect (e.g., birth defects and cancer) must have an underlying biological effect consisting of either a measurable molecular, biochemical or cellular consequence. However, not all measurable molecular, biochemical or cellular events need to lead to a health effect. DNA damage has been the primary focus of radiation targets, with either cell death (primarily, necrosis) or mutations (gene and chromosomal) as being the cellular consequence. In addition, mutagenesis of genes (oncogenes, tumor suppressor genes and DNA repair genes) has been assumed to play the major process in health consequences such as radiation-induced birth defects and cancer. To complicate the interpretation of low-level radiation exposure is the unresolved issue of ''thresholds or non-thresholds'' for both molecular and cellular biological and health effects. The lack of experimental and epidemiological data on low-level radiation and controversies related to nothreshold, linear dose responses and concepts of the ''bystander effect'', adaptive response and genomic instability will be discussed.
Evaluation of the cytotoxicity and the genotoxicity induced by α radiation in an A549 cell line
Radiation Measurements, 2011
Exposure to radon and its progenies represents one of the greatest risks of ionizing radiation from natural sources. Nowadays, these risks are assessed by the extrapolation of biological effects observed from epidemiological data. In the present study, we made a dose response curve, to evaluate the in vitro response of A549 human lung cells to a-radiation resulting from the decay of a 210 Po source, evaluated by the cytokinesis blocked micronuclei assay. The clonogenic assay was used to measure the survival cell fraction. As expected, the results revealed an increase of cellular damage with increased doses made evident from the increased number of micronuclei (MN) per binucleated cell (BN). Besides this study involving the biological effects induced by direct irradiation, and due to the fact that radiation-induced genomic instability is thought to be an early event in radiation carcinogenesis, we analyzed the genomic instability in early and delayed untargeted effects, by using the medium transfer technique. The obtained results show that unirradiated cells exposed to irradiated medium reveal a higher cellular damage in earlier effects when compared to the delayed effects. The obtained results may provide clues for the biodosimetric determination of radon dose to airway cells at cumulative exposures.
Radon in Human Environment and Carcinoma – Part 2
2017
The article describes basic theories of small doses of ionizing radiation’s impact on an organism and the current views on mechanisms of cancer emergence influenced by radiation. The risk estimation of lung carcinoma caused by inhalation of radon present in human environment was provided.
Carcinogenicity of Ionizing Radiation: A Literature Review
Onkologiâ i radiologiâ Kazahstana, 2023
Relevance: According to WHO, malignant neoplasms rank second in population mortality structure due to a constantly increasing influence of technogenic factors that have a direct carcinogenic effect on the body and suppress defense mechanisms. Ionizing radiation plays a special role in the development of cancer. It is used in industry, agriculture, medicine, and scientific research as a diagnostic tool in modern healthcare and radiation therapy for cancer treatment. The consequences of radiation influence are not only the result of a direct effect on the body but also a delayed one through generations of parents and grandparents. According to the radiobiological hypothesis, any level of radiation, no matter how small, poses a risk of long-term consequences, including cancer, in exposed people and their descendants of the first two generations. That is, cancerous tumors are likely consequences of the influence of radiation. Despite various theories of the biological effect of low doses of ionizing radiation, most authors attach primary importance to DNA damage in the manifestation of genetic effects (the concept of non-threshold mutational action). The study aimed to highlight the role of ionizing radiation in tumorigenesis. Methods: Data from MEDLINE, Embase, Scopus, PubMed, and Cochrane Central Register of Controlled Trials was analyzed to select and analyze relevant information over the past 10 years using such keywords as "gamma irradiation," "spontaneous oncogenesis," and "prevention of oncogenesis." Results: Radiation exposure may increase the risk of cancer development due to epigenetic changes leading to increased genomic instability (GI) and/or specific suppression of tumor suppressor genes. Changes in the TP53 gene network expression occur; the most significant genes as predictors of carcinogenesis are ST13, IER3, BRCAI, LRDD, and MRAS. Epigenetic changes also influence individual susceptibility to radiation-induced cancer. In addition to the mutagenic effects of ROS and AFN, there is also evidence that oxidative stress plays a fundamental role in epigenetic modifications. Conclusion: As a result of radiation exposure, damage occurs that causes genetic and epigenetic changes, leading to changes in the level of protein expression due to changes in the methylation of cytosine residues in DNA, modification of histones, and regulation of microRNA expression.
The Biophysical Stage of Radiation Carcinogenesis
Health Physics, 1988
The dependence of the induction of cancer on the absorbed dose of ionizing radiations has been specified in terms of increasing complexity. The first notion of simple proportionality (the "linear hypothesis") is now frequently replaced with a dependence on both the first and second powers of the dose (the "linear-quadratic model") which implies proportionality at low doses only. Microdosimetric considerations and in particular the'theory of dual radiation action would be in accord with this relation if tumors were to arise from single cells as the result of a transformation that is autonomous (i.e., depends only on the radiation received by the cell). In this case it must be expected that the linear portion of the dose-effect curve is dose rate independent but that the quadratic component may decrease with decreasing dose rate because of repair during the interval between two events (energy depositions by individual particles). Various data appeared to be in agreement with this picture. However it was shown some time ago that the dose-incidence relation of a neoplasm indicates a non-autonomous response because of departure from a linear dependence when the mean number of events in cells is much less than one in neutron irradiations. Another discrepancy is the repeated observation that reduction of dose rate* while resulting in the expected lessening of the effectiveness of low-LET radiation, increases the effectiveness of neutrons (especially in the case of oncogenic cell transformation). As will be shown, it is possible to •Presented at the 25th Hanford Life Sciences Symposium* 2 account for this phenomenon although at this point the limitations of the , available data make the explanation seai-quantltative and therefore still somewhat hypothetical* However, it should be noted that it does not even require a non-autonomous response and thus is at least an example of the complexities that can arise in the earliest (biophysical) stage of radiation carcinogenesis.
What Can Chemical Carcinogenesis Shed Light on the LNT Hypothesis in Radiation Carcinogenesis?
Dose-Response, 2019
To protect the public’s health from exposure to physical, chemical, and microbiological agents, it is important that any policy be based on rigorous scientifically based research. The concept of “linear no-threshold” (LNT) has been implemented to provide guideline exposures to these agents. The practical limitation to testing this hypothesis is to provide sufficient samples for experimental or epidemiological studies. While there is no universally accepted understanding of most human diseases, there seems to be better understanding of cancer that might help resolve the “LNT” model. The public’s concern, after being exposed to radiation, is the potential of producing cancer. The most rigorous hypothesis of human carcinogenesis is the “multistage, multimechanism” chemical carcinogenesis model. The radiation carcinogenesis LNT model, rarely, if ever, built it into their support. It will be argued that this multistage, multimechanism model of carcinogenesis, involving the “initiation” o...
Advances in Space Research, 2002
When applied to the Colorado Plateau miner population, the two-stage clonal expansion (TSCE) model of radiation carcinogenesis predicts that radiation-induced promotion dominates radiation-induced initiation. Thus, according to the model, at least for alpha-particle radiation from inhaled radon daughters, lung cancer induction over long periods of protracted irradiation appears to be dominated by radiation-induced modification of the proliferation kinetics of already-initiated cells rather than by direct radiation-induced initiation (i.e., mutation) of normal cells. We explore the possible consequences of this result for radiation exposures to space travelers on long missions. Still unknown is the LET dependence of this effect. Speculations of the cause of this phenomenon include the suggestion that modification of cell kinetics is caused by a "bystander" effect, i.e., the traversal of normal cells by alpha particles, followed by the signaling of these cells to nearby initiated cells which then modify their proliferation kinetics.
The Role of Radiation Induced Injury on Lung Cancer
Cancers, 2017
This manuscript evaluates the role of cell killing, tissue disorganization, and tissue damage on the induction of lung cancer following low dose rate radiation exposures from internally deposited radioactive materials. Beagle dogs were exposed by inhalation to 90 Y, 91 Y, 144 Ce, or 90 Sr in fused clay particles. Dogs lived out their life span with complete pathology conducted at the time of death. The radiation dose per cell turnover was characterized and related to the cause of death for each animal. Large doses per cell turnover resulted in acute death from lung damage with extensive cell killing, tissue disorganization, chronic inflammatory disease, fibrosis, and pneumonitis. Dogs with lower doses per cell turnover developed a very high frequency of lung cancer. As the dose per cell turnover was further decreased, no marked tissue damage and no significant change in either life span or lung cancer frequency was observed. Radiation induced tissue damage and chronic inflammatory disease results in high cancer frequencies in the lung. At doses where a high frequency of chromosome damage and mutations would be predicted to occur there was no decrease in life span or increase in lung cancer. Such research suggests that cell killing and tissue damage and the physiological responses to that damage are important mechanisms in radiation induced lung cancer.
The Effects of Radiation and Dose-Fractionation on Cancer and Non-Tumor Disease Development
International Journal of Environmental Research and Public Health, 2012
The Janus series of radiation experiments, conducted from 1970 to 1992, explored the effects of gamma and neutron radiation on animal lifespan and disease development. Data from these experiments presents an opportunity to conduct a large scale analysis of both tumor and non-tumor disease development. This work was focused on a subset of animals from the Janus series of experiments, comparing acute or fractionated exposures of gamma or neutron radiation on the hazards associated with the development of tumor and non-tumor diseases of the liver, lung, kidney or vascular system. This study also examines how the co-occurrence of non-tumor diseases may affect tumor-associated hazards. While exposure to radiation increases the hazard of dying with tumor and non-tumor diseases, dose fractionation modulates these hazards, which varies across different organ systems. Finally, the effect that concurrent non-cancer diseases have on the hazard of dying with a tumor also differs by organ system. These results highlight the complexity in the effects of radiation on the liver, lung, kidney and vascular system.