Role of Low-Level Ionizing Radiation in Multi-Step Carcinogenic Process (original) (raw)
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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.
A Nontarget Mechanism to Explain Carcinogenesis Following α-Irradiation
Dose-Response
This commentary highlights the published data on the metabolic processes that lead to the development of cancer following intakes of asbestos and chemical agents. Following exposure to both, the key initiating event is cell injury leading to cell death that may further lead to inflammation, fibrosis, and cancer. Since α-particle transits also kill cells, it is suggested that cell death and inflammation will also trigger carcinogenesis within tissues irradiated by these particles. Such an explanation would be consistent with the inflammation and fibrosis seen in tumor-bearing tissues irradiated by radon-222, radium-226, thorium-232, plutonium-239, and other α-emitting radionuclides. It would also provide an explanation for dose-related changes in latency and in the similar dose–responses for the same tissue in differently sized species.
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.
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.
Radiation Carcinogenesis in Context: How Do Irradiated Tissues Become Tumors?
Health Physics, 2009
It is clear from experimental studies that genotype is an important determinant of cancer susceptibility in general, and for radiation carcinogenesis specifically. It has become increasingly clear that genotype influences not only the ability to cope with DNA damage but also influences the cooperation of other tissues, like the vasculature and immune system, necessary for the establishment of cancer. Our experimental data and that of others suggest that the carcinogenic action of ionizing radiation (IR) can also be considered a two-compartment problem: while IR can alter genomic sequence as a result of DNA damage, it can also induce signals that alter multicellular interactions and phenotypes that underpin carcinogenesis. Rather than being accessory or secondary to genetic damage, we propose that such non-targeted radiation effects create the critical context that promotes cancer development. This review focuses on experimental studies that clearly define molecular mechanisms by which cell interactions contribute to cancer in different organs, and addresses how non-targeted radiation effects may similarly act though the microenvironment. The definition of non-targeted radiation effects and their dose dependence could modify the current paradigms for radiation risk assessment since radiation non-targeted effects, unlike DNA damage, are amenable to intervention. The implications of this perspective in terms of reducing cancer risk after exposure are discussed.
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.
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.
Radiation and Environmental Biophysics
The probability that an observed cancer was caused by radiation exposure is usually estimated using cancer rates and risk models from radioepidemiological cohorts and is called assigned share (AS). This definition implicitly assumes that an ongoing carcinogenic process is unaffected by the studied radiation exposure. However, there is strong evidence that radiation can also accelerate an existing clonal development towards cancer. In this work, we define different association measures that an observed cancer was newly induced, accelerated, or retarded. The measures were quantified exemplarily by Monte Carlo simulations that track the development of individual cells. Three biologically based two-stage clonal expansion (TSCE) models were applied. In the first model, radiation initiates cancer development, while in the other two, radiation has a promoting effect, i.e. radiation accelerates the clonal expansion of pre-cancerous cells. The parameters of the TSCE models were derived from ...
Genes, 2012
Although radiation carcinogenesis has been shown both experimentally and epidemiologically, the use of ionizing radiation is also one of the major modalities in cancer treatment. Various known cellular and molecular events are involved in carcinogenesis. Apart from the known phenomena, there could be implications for carcinogenesis and cancer prevention due to other biological processes such as the bystander effect, the abscopal effect, intrinsic radiosensitivity and radioadaptation. Bystander effects have consequences for mutation initiated cancer paradigms of radiation carcinogenesis, which provide the mechanistic justification for low-dose risk estimates. The abscopal effect is potentially important for tumor control and is mediated through cytokines and/or the immune system (mainly cell-mediated immunity). It results from loss of growth and stimulatory and/or immunosuppressive factors from the tumor. Intrinsic radiosensitivity is a feature of some cancer prone chromosomal breaka...