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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The accepted linear no-threshold (LNT) dose response for stochastic effects is not valid even for the cellular level. Published data on the human radiation carcinogenesis demonstrate now the radiation hormesis or the absence of effects or its reduction in the whole low dose interval when a dose rate is decreased. This is demonstrated for leukemia and for lung, breast, thyroid, bone, skin and liver solid cancers, for such organs, which are responsible in the more, than 1/2 of cancer detriment postulated by the ICRP. It is possible valid for the whole of solid cancers and for nontumorogenic death.
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PMID:[Features of radiation carcinogenesis in man at low doses and low dose rates]. 987 91

Radiation-induced lymphomagenesis and leukemogenesis are complex processes involving both genetic and epigenetic changes. Although genetic alterations during radiation-induced lymphoma- and leukemogenesis are fairly well studied, the role of epigenetic changes has been largely overlooked. Rodent models are valuable tools for identifying molecular mechanisms of lymphoma and leukemogenesis. A widely used mouse model of radiation-induced thymic lymphoma is characterized by a lengthy "pre-lymphoma" period. Delineating molecular changes occurring during the pre-lymphoma period is crucial for understanding the mechanisms of radiation-induced leukemia/lymphoma development. In the present study, we investigated the role of radiation-induced DNA methylation changes in the radiation carcinogenesis target organ--thymus, and non-target organ--muscle. This study is the first report on the radiation-induced epigenetic changes in radiation-target murine thymus during the pre-lymphoma period. We have demonstrated that acute and fractionated whole-body irradiation significantly altered DNA methylation pattern in murine thymus leading to a massive loss of global DNA methylation. We have also observed that irradiation led to increased levels of DNA strand breaks 6 h following the initial exposure. The majority of radiation-induced DNA strand breaks were repaired 1 month after exposure. DNA methylation changes, though, were persistent and significant radiation-induced DNA hypomethylation was observed in thymus 1 month after exposure. In sharp contrast to thymus, no significant persistent changes were noted in the non-target muscle tissue. The presence of stable DNA hypomethylation in the radiation-target tissue, even though DNA damage resulting from initial genotoxic radiation insult was repaired, suggests of the importance of epigenetic mechanisms in the development of radiation-related pathologies. The possible role of radiation-induced DNA hypomethylation in radiation-induced genome instability and aberrant gene expression in molecular etiology of thymic lymphomas is discussed.
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PMID:Stable loss of global DNA methylation in the radiation-target tissue--a possible mechanism contributing to radiation carcinogenesis? 1620 73

Thymus, an important component of hematopoietic tissue, is a well-documented "target" of radiation carcinogenesis. Both acute and fractionated irradiation result in a high risk of leukemia and thymic lymphoma. However, the exact mechanisms underlying radiation-induced predisposition to leukemia and lymphoma are still unknown, and the contributions of genetic and epigenetic mechanisms in particular have yet to be defined. Global DNA hypomethylation is a well-known characteristic of cancer cells. Recent studies have also shown that tumor cells undergo prominent changes in histone methylation, particularly a substantial loss of trimethylation of histone H4-Lys20 and demethylation of genomic DNA. These losses are considered a universal marker of malignant transformation. In the present study, we investigated the effect of low-dose radiation exposure on the accumulation of DNA lesions and alterations of DNA methylation and histone H4-Lys20 trimethylation in the thymus tissue using an in vivo murine model. For the first time, we show that fractionated whole-body application of 0.5 Gy X-ray leads to decrease in histone H4-Lys20 trimethylation in the thymus. The loss of histone H4-Lys20 trimethylation was accompanied by a significant decrease in global DNA methylation as well as the accumulation of DNA damage as monitored by persistence of histone gammaH2AX foci in the thymus tissue of mice exposed to fractionated irradiation. Altered DNA methylation was associated with reduced expression of maintenance (DNMT1) and, to a lesser extent, de novo DNA methyltransferase DNMT3a in exposed animals. Expression of another de novo DNA methyltransferase DNMT3b was decreased only in males. Irradiation also resulted in approximately 20% reduction in the levels of methyl-binding proteins MeCP2 and MBD2. Our results show the involvement of epigenetic alterations in radiation-induced responses in vivo. These changes may play a role in genome destabilization that ultimately leads to cancer.
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PMID:Fractionated low-dose radiation exposure leads to accumulation of DNA damage and profound alterations in DNA and histone methylation in the murine thymus. 1625 89

Cigarette smoking, which is presently associated with more than 20% of adult deaths in the United States, is a large confounder to radiation risk estimates derived from epidemiology data. Astronauts and other exposed groups are classified as never-smokers (NS), defined as lifetime use of less than 100 cigarettes. In the past, radiation risk estimates have been made using average U.S. population rates for cancer and all causes of death, which may lead to overestimation of radiation risks for NS. In this report, age- and gender-specific radiation carcinogenesis risk calculations for NS and the average U.S. population are compared. Lung is the major tissue site for smoking and radiation-related cancer. However, other radiogenic cancers where tobacco has been shown to increase population cancer rates are esophagus, oral cavity, salivary gland, bladder, stomach, liver, colorectal, and leukemia. After adjusting U.S. cancer rates to remove smoking effects, radiation risks for lung and other cancers were estimated using the multiplicative risk model and a mixture model, with weighted contributions for additive and multiplicative risk transfer. Radiation mortality risks for NS were reduced compared to the average U.S. population by more than 20% and 50% in the mixture model and multiplicative transfer models, respectively. The authors discuss possible mechanisms of cancer risks from radiation and tobacco that suggest multiplicative effects could occur. These results suggest that improved understanding of possible synergisms between cancer initiators and promoters, such as radiation and tobacco, would greatly improve risk estimates and reduce uncertainties for differentially exposed groups, including NS.
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PMID:Radiation carcinogenesis risk assessments for never-smokers. 2303 94

The last decade has introduced a new era of epidemiologic studies of low-dose radiation facilitated by electronic record linkage and pooling of cohorts that allow for more direct and powerful assessments of cancer and other stochastic effects at doses below 100 mGy. Such studies have provided additional evidence regarding the risks of cancer, particularly leukemia, associated with lower-dose radiation exposures from medical, environmental, and occupational radiation sources, and have questioned the previous findings with regard to possible thresholds for cardiovascular disease and cataracts. Integrated analysis of next generation genomic and epigenetic sequencing of germline and somatic tissues could soon propel our understanding further regarding disease risk thresholds, radiosensitivity of population subgroups and individuals, and the mechanisms of radiation carcinogenesis. These advances in low-dose radiation epidemiology are critical to our understanding of chronic disease risks from the burgeoning use of newer and emerging medical imaging technologies, and the continued potential threat of nuclear power plant accidents or other radiological emergencies.
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PMID:A New Era of Low-Dose Radiation Epidemiology. 2623 1

Previous analyses in a cohort of Chornobyl cleanup workers revealed significantly increased radiation-related risk for all leukemia types, including chronic lymphocytic leukemia (CLL). Numerous investigations emphasized the significance of genetic susceptibility to the radiation carcinogenesis. The aim of the work was to study the distribution of TP53 single nucleotide polymorphisms (SNPs) in CLL patients exposed to ionizing radiation (IR) due to Chornobyl nuclear power plant accident and estimate their impact on disease development.
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PMID:The distribution of TP53 gene polymorphisms in chronic lymphocytic leukemia patients, sufferers of Chornobyl nuclear power plant accident. 2823 Aug 20

During the past three decades, the deleterious consequences of Chornobyl accident including carcinogenic effects in the people who were accidentally exposed to radiation have been intensively studied. In particular, recent studies provided increased knowledge of the molecular pathogenesis of thyroid tumors in children exposed to Chornobyl fallout. The risk of several forms of leukemia including myelodysplastic syndromes is elevated in Chornobyl liquidators. Furthermore, the upward trends of increases in a variety of other tumors including breast cancer, cancers of central nervous system and renal cancer have been reported in the persons exposed to Chornobyl fallout. There is growing evidence that insufficient apoptosis allows irradiated cells to survive and thereby contributes to carcinogenesis. The purpose of the present survey is to summarize the recent findings related to apoptotic biomarkers among cancer patients from the different populations affected by the Chornobyl catastrophe. Among the particularly radiosensitive cancer sites, we focused on thyroid cancer and leukemia. Several genes and/or proteins controlling apoptosis directly or indirectly have been incorporated into the analysis. The data reviewed here provide a mechanistic link between the apoptosis alterations and development of radiation-related cancer in the 30-year post-Chornobyl period. We suggest that the type of mutations arising from misrepair of DNA double strand breaks (gene fusion and amplification) is the initial signature event in radiation-induced thyroid cancer. Much work has to be done over the next years to elucidate central questions related to the nature of human radiation carcinogenesis. This article is part of a Special Issue entitled "The Chornobyl Nuclear Accident: Thirty Years After".
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PMID:Molecular markers of apoptosis in cancer patients exposed to ionizing radiation: the post-Chornobyl view. 2823 Aug 25


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