An Examination of Radiation Hormesis Mechanisms Using a Multistage Carcinogenesis Model

Schöllnberger, Helmut; Stewart, Robert D.; Mitchel, R. E. J.; Hofmann, Werner

doi:10.1080/15401420490900263

Cited by 21 publications

(23 citation statements)

References 153 publications

(240 reference statements)

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“…These results are consistent with knowledge to date on radiation‐induced cellular effects. It has been shown that key components of the radiation‐induced response include the elimination of aberrant cells through apoptosis and induction of cell cycle arrest, followed by DNA‐repair, activation of immune functions and compensatory cell proliferation [reviewed in Prekeges, ; Schollnberger et al, ; Feinendegen, ; Scott and Di Palma, ; Liu, ]. In addition to providing insight into the underlying biological response of radiation, by ranking the pathways based on BMD values a list of genes that may respond to low versus high doses of radiation was also identified (Table ), providing targets to support low dose risk assessment.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional benchmark dose modeling: Exploring how advances in chemical risk assessment may be applied to the radiation field

Chauhan

Kuo

McNamee

et al. 2016

Environ and Mol Mutagen

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Recent advances in “‐omics” technologies have simplified capacity to concurrently assess expression profiles of thousands of targets in a cellular system. However, compilation and analysis of “omics” data in support of human health protection remains a challenge. Benchmark dose (BMD) modeling is currently being employed in chemical risk assessment to estimate acceptable levels of exposure. Although typically applied to conventional endpoints, newer software has enabled this application to be extended to transcriptomic datasets. BMD analytical tools now have the capacity to model transcriptional dose‐response data to derive meaningful BMD values for genes, pathways and gene ontologies. In this report, radiation data obtained from the Gene Expression Omnibus (GEO) were analyzed to generate BMD values for transcriptional responses. The datasets comprised microarray analyses of human blood gamma‐irradiated ex vivo (0–20 Gy) and human‐derived cell lines exposed to alpha particle radiation (0.5–1.5 Gy). The distributions of BMDs for statistically significant genes and pathways in response to radiation exposure were examined and compared across studies. BMD modeling could identify pathway/gene sensitivities across wide radiation dose ranges, experimental conditions (time‐points, cell types) and radiation qualities. BMD analysis offered a new approach to examine transcriptional data. The results were shown to provide information on transcriptional thresholds of effects to support refined risk assessments for low dose ionizing radiation exposures, derive gene‐based values for relative biological effectiveness and identify pathways involved in radiation sensitivities across cell types which may extend to applications a clinical setting. Environ. Mol. Mutagen. 57:589–604, 2016. © 2016 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 99%

Transcriptional benchmark dose modeling: Exploring how advances in chemical risk assessment may be applied to the radiation field

Chauhan

Kuo

McNamee

et al. 2016

Environ and Mol Mutagen

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“…∑iendo is the expected number of i th type (simple or complex) of lesions created by endogenous processes (cell −1 year −1 ), ∑irad is the expected number of i th type lesions created by radiation (mGy −1 cell −1 ) and λ i (year −1 ) is the rate of lesion removal (correct or incorrect repair). Values for these model parameters have been given (Schöllnberger et al, 2004). The values for λ sl and λ cl are 18,228 yr −1 (repair half-time of 20 min) and 3,038 yr −1 (repair half-time of 2 hr), respectively.…”

Section: Methodsmentioning

confidence: 99%

“…The current study is an extension of an ongoing collaborative effort, with the aim to improve model-based risk estimations for low doses of low-LET radiation. Earlier studies were restricted to low-LET radiation delivered at low dose rates (Schöllnberger et al, 2004; Schöllnberger et al, in press). As in the previous work, the new model accounts for simple and complex damage formed by endogenous processes and ionising radiation.…”

Section: Introductionmentioning

confidence: 99%

A model for low dose effects of low-LET radiation delivered at high dose rates

Schöllnberger

Stewart

Mitchel

2006

IJLR

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In vitro studies show that protective tumour-reducing effects occur for low dose rates (mGy per minute). To account for these phenomena, we have previously developed stochastic and deterministic multi-stage cancer models that include radiation-induced adaptations in DNA repair processes and radical scavenging. Here, these models are extended to account for the induction of radioprotective mechanisms for low doses of low LET radiation delivered at high dose rates. Cellular adaptations in DNA repair are related to temporal changes in the amount of DNA damage in a cell. The combined effects of endogenous DNA damage, background radiation and artificial irradiation are considered.

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“…Yet, under this scenario, at the mechanistic level, beneficial effects of toxins in low concentrations can be the result of compensatory biological processes following an initial disruption in homeostasis ("homeostatic overcompensation," Calabrese & Baldwin, 2002). At the cellular level, this overcompensation phenomenon includes processes associated with receptor/signaling mechanisms (Calabrese, 2013), DNA damage repair (Schöllnberger, Stewart, Mitchel, & Hofmann, 2004), immunefunction enhancement (Cui et al, 2017), and alteration of gene expression (Sokolov & Neumann, 2015). As epigenetic mechanisms have also been described for hormetic effects (Vaiserman, 2011), a link to environmental matching theory can be made (Kaiser, 2003).…”

Section: Avail Ab Le Me Thods and Promis Ing Re S E Arch Avenue Smentioning

confidence: 99%

Turning natural adaptations to oncogenic factors into an ally in the war against cancer

Vittecoq

Giraudeau

Sepp

et al. 2018

Evolutionary Applications

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Both field and experimental evolution studies have demonstrated that organisms naturally or artificially exposed to environmental oncogenic factors can, sometimes rapidly, evolve specific adaptations to cope with pollutants and their adverse effects on fitness. Although numerous pollutants are mutagenic and carcinogenic, little attention has been given to exploring the extent to which adaptations displayed by organisms living in oncogenic environments could inspire novel cancer treatments, through mimicking the processes allowing these organisms to prevent or limit malignant progression. Building on a substantial knowledge base from the literature, we here present and discuss this progressive and promising research direction, advocating closer collaboration between the fields of medicine, ecology, and evolution in the war against cancer.

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An Examination of Radiation Hormesis Mechanisms Using a Multistage Carcinogenesis Model

Cited by 21 publications

References 153 publications

Transcriptional benchmark dose modeling: Exploring how advances in chemical risk assessment may be applied to the radiation field

Transcriptional benchmark dose modeling: Exploring how advances in chemical risk assessment may be applied to the radiation field

A model for low dose effects of low-LET radiation delivered at high dose rates

Turning natural adaptations to oncogenic factors into an ally in the war against cancer

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