Enhanced Expression of Radiation-induced Leukocyte <i>CDKN1A mRNA</i> in Multiple Primary Breast Cancer Patients: Potential New Marker of cancer susceptibility

Mitsuhashi, Masato; Peel, David; Ziogas, Argyrios; Anton‐Culver, Hoda

doi:10.4137/bmi.s3774

Cited by 6 publications

(4 citation statements)

References 21 publications

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“…We found a dose-dependent increase in the expression of the CDKN1A and BBC3 genes in bone marrow cells of mice irradiated with 12 C ions in the Bragg peak (Figure 3). Similar results were obtained on blood cells of humans and mice after X-and gammairradiation in vitro, ex vivo, and in vivo (Mitsuhashi et al 2009;Rezaeejam et al 2015). Mitsuhashi and colleagues (2009) observed a full similarity between the degrees of induction of CDKN1A and BBC3 mRNA expression after gamma-irradiation of human blood at doses of 0.1, 1.0, and 10 Gy.…”

Section: Discussionsupporting

confidence: 73%

DNA damage in blood leukocytes from mice irradiated with accelerated carbon ions with an energy of 450 MeV/nucleon

Kuznetsova

Сирота

Mitroshina

et al. 2020

International Journal of Radiation Biology

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Purpose: The objective of the study was to estimate the DNA damage in blood leukocytes at long terms after irradiation of mice with carbon ions (450 MeV/nucleon) both before and in the Bragg peak. Materials and methods: White outbred SHK male mice were exposed to whole-body irradiation with carbon ions at doses of 0.1-2 Gy in the spread-out Bragg peak and at a dose of 6 Gy before and in the Bragg peak. At different times after irradiation (1-75 days), whole blood was collected from the tail of each mouse and analyzed by the comet assay. Mice X-irradiated in the same dose range served as a positive control. The level of the expression of mRNA of CDKN1A, APEX1, BBC3, TXN2, and b-ACT genes in bone marrow cells was determined in animals irradiated with carbon ions at doses of 0.1-2 Gy using the real-time PCR. Results: It was found that, 24 h after 12 C-irradiation, a dose-dependent (0.1-2 Gy) increase in the DNA damage of leukocytes occurred, which was accompanied by a decrease in their concentration and an increase in the expression of the CDKN1A and BBC3 genes in bone marrow cells. The expression of the APEX1 and TXN2 genes did not change. In mice 12 C-irradiated at a dose of 6 Gy before and in the Bragg peak, the level of DNA damage changed as follows: by day 3, it increased; by day 23 it returned to the control level; by day 30, it increased again; and by day 75, it fell to the control level on irradiation before the Bragg peak and was significantly higher (p < .05) than in the control after irradiation in the Bragg peak. Conclusions: The dynamics of changes in the level of DNA damage in leucocytes of 12 C-irradiated mice within 30 days is similar to that in mice exposed to sublethal doses of X-radiation. The retention of the high level of DNA damage by day 75 after 12 C-irradiation in the Bragg peak indicates a significant injury of cells from different cell pools of the blood system. The high level of DNA damage may be related not only to complex DNA injuries but also to chronic oxidative stress.

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Section: Discussionsupporting

confidence: 73%

DNA damage in blood leukocytes from mice irradiated with accelerated carbon ions with an energy of 450 MeV/nucleon

Kuznetsova

Сирота

Mitroshina

et al. 2020

International Journal of Radiation Biology

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“…It is supposed that the difference of testing mode, primary design of CDKN1A gene composition and application of the primaries might be responsible for the diversity of the results. For example, Mitsuhashi et al [39] reported that multiple primary applications in CDKN1A gene composition showed higher induction of CDKN1A mRNA than single primary and control groups when leukocytes from multiple primary breast cancer patients were irradiated. The difference of mouse strain in experiment, exposure and treatment methods of the sample are also factors resulting in diversity of CDKN1A mRNA results.…”

Section: Discussionmentioning

confidence: 99%

Radiation dose effect of DNA repair-related gene expression in mouse white blood cells

Wang

Chen

et al. 2011

Med Sci Monit

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SummaryBackgroundThe aim of this study was to screen molecular biomarkers for biodosimetry from DNA repair-related gene expression profiles.Material/MethodsMice were subjected to whole-body exposure with 60Co γ rays with a dose range of 0–8 Gy at a dose rate of 0.80 Gy/min. RNA was extracted from the peripheral blood of irradiated mice at 4, 8, 12, 24 and 48hrs post-irradiation. The mRNA transcriptional changes of 11 genes related to DNA damage and repair were detected using real-time quantitative polymerase chain reaction (RT-PCR).ResultsOf the 11 genes examined, CDKN1A (cyclin-dependent kinase inhibitor 1A or p21, Cip1) and ATM (ataxia telangiectasia mutated) expression levels were found to be heavily up- and down-regulated, respectively, with exposure dose increasing at different post-irradiation times. RAD50 (RAD50 homolog), PLK3 (polo-like kinase 3), GADD45A (growth arrest and DNA damage-inducible, alpha), DDB2 (damage-specific DNA-binding protein 2), BBC3 (BCL2-binding component 3) and IER5 (immediate early response 5) gene expression levels were found to undergo significant oscillating changes over a broad dose range of 2–8 Gy at post-exposure time points observed. Three of the genes were found not to change within the observed exposure dose and post-radiation time ranges.ConclusionsThe results of this study add to the biodosimetry with biomarker data pool and will be helpful for constructing appropriate gene expression biomarker systems to evaluate radiation exposure doses.

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“…IFIT2 inhibits migration and proliferation in squamous cell carcinoma cultures [ 41 ]. IFIT1 was one of a small group of genes that predict carcinogenesis after training on DNA-damage response [ 40 ], while STARD13 is upregulated in human lymphocytes following gamma-irradiation [ 51 ], suggesting that IFIT1 may be a downstream target of STARD13 following DNA damage.…”

Section: Discussionmentioning

confidence: 99%

Co-regulatory expression quantitative trait loci mapping: method and application to endometrial cancer

Kompass

Witte

2011

BMC Med Genomics

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BackgroundExpression quantitative trait loci (eQTL) studies have helped identify the genetic determinants of gene expression. Understanding the potential interacting mechanisms underlying such findings, however, is challenging.MethodsWe describe a method to identify the trans-acting drivers of multiple gene co-expression, which reflects the action of regulatory molecules. This method-termed co-regulatory expression quantitative trait locus (creQTL) mapping-allows for evaluation of a more focused set of phenotypes within a clear biological context than conventional eQTL mapping.ResultsApplying this method to a study of endometrial cancer revealed regulatory mechanisms supported by the literature: a creQTL between a locus upstream of STARD13/DLC2 and a group of seven IFNβ-induced genes. This suggests that the Rho-GTPase encoded by STARD13 regulates IFNβ-induced genes and the DNA damage response.ConclusionsBecause of the importance of IFNβ in cancer, our results suggest that creQTL may provide a finer picture of gene regulation and may reveal additional molecular targets for intervention. An open source R implementation of the method is available at http://sites.google.com/site/kenkompass/.

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Enhanced Expression of Radiation-induced Leukocyte CDKN1A mRNA in Multiple Primary Breast Cancer Patients: Potential New Marker of cancer susceptibility

Cited by 6 publications

References 21 publications

DNA damage in blood leukocytes from mice irradiated with accelerated carbon ions with an energy of 450 MeV/nucleon

DNA damage in blood leukocytes from mice irradiated with accelerated carbon ions with an energy of 450 MeV/nucleon

Radiation dose effect of DNA repair-related gene expression in mouse white blood cells

Co-regulatory expression quantitative trait loci mapping: method and application to endometrial cancer

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