Cellular burdens and biological effects on tissue level caused by inhaled radon progenies

Madas, Balázs G.; Balásházy, Imre; Farkas, Árpád; Szőke, István

doi:10.1093/rpd/ncq522

Cited by 13 publications

(6 citation statements)

References 8 publications

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“…Alpha radiation releases a large amount of energy in a very short linear track alpha (high-energy transfer capacity, HET), which is more biologically significant than either beta or gamma radiations and reacts much more readily with deoxyribonucleic acid (DNA), generating oxidative stress (reactive oxygen species, ROS) and hydroxyl radical attack through radiolysis, despite their reduced penetrating capability [44][45][46][47].…”

Section: Genomic Effects Of Alpha Radiationmentioning

confidence: 99%

Radon and Lung Cancer: Current Trends and Future Perspectives

Riudavets

Herreros

Besse

et al. 2022

Cancers

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Lung cancer is a public health problem and the first cause of cancer death worldwide. Radon is a radioactive gas that tends to accumulate inside homes, and it is the second lung cancer risk factor after smoking, and the first one in non-smokers. In Europe, there are several radon-prone areas, and although the 2013/59 EURATOM directive is aimed to regulate indoor radon exposition, regulating measures can vary between countries. Radon emits alpha-ionizing radiation that has been linked to a wide variety of cytotoxic and genotoxic effects; however, the link between lung cancer and radon from the genomic point of view remains poorly described. Driver molecular alterations have been recently identified in non-small lung cancer (NSCLC), such as somatic mutations (EGFR, BRAF, HER2, MET) or chromosomal rearrangements (ALK, ROS1, RET, NTRK), mainly in the non-smoking population, where no risk factor has been identified yet. An association between radon exposure and oncogenic NSCLC in non-smokers has been hypothesised. This paper provides a practical, concise and updated review on the implications of indoor radon in lung cancer carcinogenesis, and especially of its potential relation with NSCLC with driver genomic alterations.

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Section: Genomic Effects Of Alpha Radiationmentioning

confidence: 99%

Radon and Lung Cancer: Current Trends and Future Perspectives

Riudavets

Herreros

Besse

et al. 2022

Cancers

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show abstract

“…The role of radon and its radioactive decay products as human carcinogens has been established by epidemiologic studies in humans [27]. It is well demonstrated that radon induces DNA mutations and subsequential functional damage [28]. The high-linear energy transfer of α-particles emitted by radon and radon decay products can directly attack genomic DNA and cause mainly double-strand breaks in DNA [29].…”

Section: Toxic Effects Of Exposure To Radon In Humanmentioning

confidence: 99%

Radon Biomonitoring and microRNA in Lung Cancer

Bersimbaev

Pulliero

Bulgakova

et al. 2020

IJMS

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Radon is the number one cause of lung cancer in non-smokers. microRNA expression in human bronchial epithelium cells is altered by radon, with particular reference to upregulation of miR-16, miR-15, miR-23, miR-19, miR-125, and downregulation of let-7, miR-194, miR-373, miR-124, miR-146, miR-369, and miR-652. These alterations alter cell cycle, oxidative stress, inflammation, oncogene suppression, and malignant transformation. Also DNA methylation is altered as a consequence of miR-29 modification induced by radon. Indeed miR-29 targets DNA methyltransferases causing inhibition of CpG sites methylation. Massive microRNA dysregulation occurs in the lung due to radon expose and is functionally related with the resulting lung damage. However, in humans this massive lung microRNA alterations only barely reflect onto blood microRNAs. Indeed, blood miR-19 was not found altered in radon-exposed subjects. Thus, microRNAs are massively dysregulated in experimental models of radon lung carcinogenesis. In humans these events are initially adaptive being aimed at inhibiting neoplastic transformation. Only in case of long-term exposure to radon, microRNA alterations lead towards cancer development. Accordingly, it is difficult in human to establish a microRNA signature reflecting radon exposure. Additional studies are required to understand the role of microRNAs in pathogenesis of radon-induced lung cancer.

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“…The heterogeneous aerosol deposition results in heterogeneous spatial activity distribution of inhaled radon progeny in the bronchial airways [3]. Due to the short range of emitted alphaparticles and the relatively short half life of radon progeny, the heterogeneity is reflected in the dose distributions too [4]. Whereas it remains an open question whether the measure of dose heterogeneity increases or decreases the risk, the understanding of the mechanisms leading from radon exposure to lung cancer is not expected if the effects of locally high doses are not studied [5].…”

Section: Introductionmentioning

confidence: 99%

Radon induced hyperplasia: effective adaptation reducing the local doses in the bronchial epithelium

Madas¹

2016

J. Radiol. Prot.

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There is experimental and histological evidence that chronic irritation and cell death may cause hyperplasia in the exposed tissue. As the heterogeneous deposition of inhaled radon progeny results in high local doses at the peak of the bronchial bifurcations, it was proposed earlier that hyperplasia occurs in these deposition hot spots upon chronic radon exposure. The objective of the present study is to quantify how the induction of basal cell hyperplasia modulates the microdosimetric consequences of a given radon exposure. For this purpose, computational epithelium models were constructed with spherical cell nuclei of six different cell types based on histological data. Basal cell hyperplasia was modelled by epithelium models with additional basal cells and increased epithelium thickness. Microdosimetry for alpha-particles was performed by an own-developed Monte-Carlo code. Results show that the average tissue dose, and the average hit number and dose of basal cells decrease by the increase of the measure of hyperplasia. Hit and dose distribution reveal that the induction of hyperplasia may result in a basal cell pool which is shielded from alpha-radiation. It highlights that the exposure history affects the microdosimetric consequences of a present exposure, while the biological and health effects may also depend on previous exposures. The induction of hyperplasia can be considered as a radioadaptive response at the tissue level. Such an adaptation of the tissue challenges the validity of the application of the dose and dose rate effectiveness factor from a mechanistic point of view. As the location of radiosensitive target cells may change due to previous exposures, dosimetry models considering the tissue geometry characteristic of normal conditions may be inappropriate for dose estimation in case of protracted exposures. As internal exposures are frequently chronic, such changes in tissue geometry may be highly relevant for other incorporated radionuclides.

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Cellular burdens and biological effects on tissue level caused by inhaled radon progenies

Cited by 13 publications

References 8 publications

Radon and Lung Cancer: Current Trends and Future Perspectives

Radon and Lung Cancer: Current Trends and Future Perspectives

Radon Biomonitoring and microRNA in Lung Cancer

Radon induced hyperplasia: effective adaptation reducing the local doses in the bronchial epithelium

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