Combined exposure to X-irradiation followed by N-ethyl-N-nitrosourea treatment alters the frequency and spectrum of Ikaros point mutations in murine T-cell lymphoma

Kakinuma, Shizuko; Nishimura, Masaharu; Amasaki, Yoshiko; Takada, Mayumi; Yamauchi, K.; Sudo, Satomi; Shang, Yi; Doi, Kazutaka; Yoshinaga, Shinji; Shimada, Yoshiya

doi:10.1016/j.mrfmmm.2012.06.001

Cited by 9 publications

(6 citation statements)

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“…As an experimental model, we used mice administered either sake or ethanol that were then exposed to fractionated irradiation (0.75 Gy, 4 times). Fractionated irradiation with approximately 0.75 Gy has been performed at various intervals in several studies [ 51 – 53 ]. The dose per fraction used here was similar to the lowest value used in a report evaluating the combined effects of radiation and chemical treatment on carcinogenesis [ 51 ].…”

Section: Resultsmentioning

confidence: 99%

“…Fractionated irradiation with approximately 0.75 Gy has been performed at various intervals in several studies [ 51 – 53 ]. The dose per fraction used here was similar to the lowest value used in a report evaluating the combined effects of radiation and chemical treatment on carcinogenesis [ 51 ]. Compared to single irradiation, fractionated irradiation increases the potential that radiation-related effects that are altered in response to chronic sake administration can be detected.…”

Section: Resultsmentioning

confidence: 99%

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Chronic Intake of Japanese Sake Mediates Radiation-Induced Metabolic Alterations in Mouse Liver

Nakajima¹,

Varès²,

Wang³

et al. 2016

PLoS ONE

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Sake is a traditional Japanese alcoholic beverage that is gaining popularity worldwide. Although sake is reported to have beneficial health effects, it is not known whether chronic sake consumption modulates health risks due to radiation exposure or other factors. Here, the effects of chronic administration of sake on radiation-induced metabolic alterations in the livers of mice were evaluated. Sake (junmai-shu) was administered daily to female mice (C3H/He) for one month, and the mice were exposed to fractionated doses of X-rays (0.75 Gy/day) for the last four days of the sake administration period. For comparative analysis, a group of mice were administered 15% (v/v) ethanol in water instead of sake. Metabolites in the liver were analyzed by capillary electrophoresis-time-of-flight mass spectrometry one day following the last exposure to radiation. The metabolite profiles of mice chronically administered sake in combination with radiation showed marked changes in purine, pyrimidine, and glutathione (GSH) metabolism, which were only partially altered by radiation or sake administration alone. Notably, the changes in GSH metabolism were not observed in mice treated with radiation following chronic administration of 15% ethanol in water. Changes in several metabolites, including methionine and valine, were induced by radiation alone, but were not detected in the livers of mice who received chronic administration of sake. In addition, the chronic administration of sake increased the level of serum triglycerides, although radiation exposure suppressed this increase. Taken together, the present findings suggest that chronic sake consumption promotes GSH metabolism and anti-oxidative activities in the liver, and thereby may contribute to minimizing the adverse effects associated with radiation.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Chronic Intake of Japanese Sake Mediates Radiation-Induced Metabolic Alterations in Mouse Liver

Nakajima¹,

Varès²,

Wang³

et al. 2016

PLoS ONE

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“…The low doses of low-LET radiation alone reduce spontaneously occurring chromosome aberrations and malignant transformation in cultured mammalian cells [31–34]. Moreover, irradiation of mice with low dose, or low dose-rate, γ-rays has been reported to suppress spontaneously occurring as well as chemical-induced mutations and tumors [35–42]. All available evidence points the possibility that low-doses of low-LET radiation activate a sustained-response, error-free DNA repair system.…”

Section: Discussionmentioning

confidence: 99%

Cancer risk at low doses of ionizing radiation: artificial neural networks inference from atomic bomb survivors

Sasaki

Tachibana

Takeda

2013

Journal of Radiation Research

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Cancer risk at low doses of ionizing radiation remains poorly defined because of ambiguity in the quantitative link to doses below 0.2 Sv in atomic bomb survivors in Hiroshima and Nagasaki arising from limitations in the statistical power and information available on overall radiation dose. To deal with these difficulties, a novel nonparametric statistics based on the ‘integrate-and-fire’ algorithm of artificial neural networks was developed and tested in cancer databases established by the Radiation Effects Research Foundation. The analysis revealed unique features at low doses that could not be accounted for by nominal exposure dose, including (i) the presence of a threshold that varied with organ, gender and age at exposure, and (ii) a small but significant bumping increase in cancer risk at low doses in Nagasaki that probably reflects internal exposure to 239Pu. The threshold was distinct from the canonical definition of zero effect in that it was manifested as negative excess relative risk, or suppression of background cancer rates. Such a unique tissue response at low doses of radiation exposure has been implicated in the context of the molecular basis of radiation–environment interplay in favor of recently emerging experimental evidence on DNA double-strand break repair pathway choice and its epigenetic memory by histone marking.

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“…In these cases, the hormones or inflammation in the mammary gland may modify the stromal environment to increase the likelihood of cellular proliferation, which amplifies the existing mutated cells and generates new mutations. Some evidence points to a protective effect of lower dose IR on chromosomal damage, mutation, and transformation in vitro (Azzam et al 2016;Elmore et al 2008;Ina et al 2005;Kakinuma et al 2012;Sakai et al 2006;Sasaki et al 2002;Shin et al 2010;Wolff et al 1988;Yamauchi et al 2008) and chromosomal damage, mutation and thymic lymphomas, and skin cancer in vivo (Ina et al 2005;Kakinuma et al 2012;Sakai et al 2006;Shin et al 2010;Yamauchi et al 2008). However, the dose range at which protection is observed varies greatly between target tissue, animal models, and other experimental conditions, suggesting that the protection is not a fixed or immutable response (Tang and Loke 2015).…”

Section: Data Gaps and Uncertaintiesmentioning

confidence: 99%

Adverse outcome pathways for ionizing radiation and breast cancer involve direct and indirect DNA damage, oxidative stress, inflammation, genomic instability, and interaction with hormonal regulation of the breast

Helm

Rudel

2020

Arch Toxicol

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Knowledge about established breast carcinogens can support improved and modernized toxicological testing methods by identifying key mechanistic events. Ionizing radiation (IR) increases the risk of breast cancer, especially for women and for exposure at younger ages, and evidence overall supports a linear dose-response relationship. We used the Adverse Outcome Pathway (AOP) framework to outline and evaluate the evidence linking ionizing radiation with breast cancer from molecular initiating events to the adverse outcome through intermediate key events, creating a qualitative AOP. We identified key events based on review articles, searched PubMed for recent literature on key events and IR, and identified additional papers using references. We manually curated publications and evaluated data quality. Ionizing radiation directly and indirectly causes DNA damage and increases production of reactive oxygen and nitrogen species (RONS). RONS lead to DNA damage and epigenetic changes leading to mutations and genomic instability (GI). Proliferation amplifies the effects of DNA damage and mutations leading to the AO of breast cancer. Separately, RONS and DNA damage also increase inflammation. Inflammation contributes to direct and indirect effects (effects in cells not directly reached by IR) via positive feedback to RONS and DNA damage, and separately increases proliferation and breast cancer through pro-carcinogenic effects on cells and tissue. For example, gene expression changes alter inflammatory mediators, resulting in improved survival and growth of cancer cells and a more hospitable tissue environment. All of these events overlap at multiple points with events characteristic of "background" induction of breast carcinogenesis, including hormone-responsive proliferation, oxidative activity, and DNA damage. These overlaps make the breast particularly susceptible to ionizing radiation and reinforce that these biological activities are important characteristics of carcinogens. Agents that increase these biological processes should be considered potential breast carcinogens, and predictive methods are needed to identify chemicals that increase these processes. Techniques are available to measure RONS, DNA damage and mutation, cell proliferation, and some inflammatory proteins or processes. Improved assays are needed to measure GI and chronic inflammation, as well as the interaction with hormonally driven development and proliferation. Several methods measure diverse epigenetic changes, but it is not clear which changes are relevant to breast cancer. In addition, most toxicological assays are not conducted in mammary tissue, and so it is a priority to evaluate if results from other tissues are generalizable to breast, or to conduct assays in breast tissue. Developing and applying these assays to identify exposures of concern will facilitate efforts to reduce subsequent breast cancer risk.Biological systems studied This review article summarizes and synthesizes data from cell-culture, experimental animals, and human epidem...

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Combined exposure to X-irradiation followed by N-ethyl-N-nitrosourea treatment alters the frequency and spectrum of Ikaros point mutations in murine T-cell lymphoma

Cited by 9 publications

References 40 publications

Chronic Intake of Japanese Sake Mediates Radiation-Induced Metabolic Alterations in Mouse Liver

Chronic Intake of Japanese Sake Mediates Radiation-Induced Metabolic Alterations in Mouse Liver

Cancer risk at low doses of ionizing radiation: artificial neural networks inference from atomic bomb survivors

Adverse outcome pathways for ionizing radiation and breast cancer involve direct and indirect DNA damage, oxidative stress, inflammation, genomic instability, and interaction with hormonal regulation of the breast

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