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  1. Article ; Online: Modifiers of radiation effects on breast cancer incidence revealed by a reanalysis of archival data of rat experiments.

    Imaoka, Tatsuhiko / Nishimura, Mayumi / Daino, Kazuhiro / Kakinuma, Shizuko

    Journal of radiation research

    2023  Volume 64, Issue 2, Page(s) 273–283

    Abstract: Cancer risk after exposure to ionizing radiation can vary between individuals and populations, but the impact of factors governing those variations is not well understood. We previously conducted a series of carcinogenesis experiments using a rat model ... ...

    Abstract Cancer risk after exposure to ionizing radiation can vary between individuals and populations, but the impact of factors governing those variations is not well understood. We previously conducted a series of carcinogenesis experiments using a rat model of breast cancer, in which 1654 rats born in 2002-2012 were exposed to γ rays at various doses and ages with or without non-radiation factors including high-fat diet, parity and chemical carcinogens. We herein reanalyze the incidence data from these archival experiments to clarify the effect of age at exposure, attained age, radiation dose and non-radiation factors (i.e. fat, parity, chemicals and birth cohorts) on radiation-related mammary cancer incidence. The analysis used excess relative risk (ERR) and excess absolute risk (EAR) models as well as generalized interaction models. Age-at-exposure dependence displayed a peak of susceptibility at puberty in both the ERR and EAR models. Attained age decreased ERR and increased EAR per unit radiation dose. The dose response was concordant with a linear model. Dietary fat exhibited a supra-multiplicative interaction, chemicals represented a multiplicative interaction, and parity and birth cohorts displayed interactions that did not significantly depart from additivity or multiplicativity. Treated as one entity, the four non-radiation factors gave a multiplicative interaction, but separation of the four factors significantly improved the fit of the model. Thus, the present study supports age and dose dependence observed in epidemiology, indicates heterogenous interactions between radiation and various non-radiation factors, and suggests the potential use of more flexible interaction modeling in radiological protection.
    MeSH term(s) Rats ; Animals ; Incidence ; Neoplasms, Radiation-Induced/epidemiology ; Neoplasms, Radiation-Induced/etiology ; Risk ; Carcinogenesis ; Carcinogens
    Chemical Substances Carcinogens
    Language English
    Publishing date 2023-01-09
    Publishing country England
    Document type Journal Article
    ZDB-ID 603983-2
    ISSN 1349-9157 ; 0449-3060
    ISSN (online) 1349-9157
    ISSN 0449-3060
    DOI 10.1093/jrr/rrac090
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Arsenite-induced Radiosensitization of Glioma Cells Is Dependent on p53 Deficiency.

    Ninomiya, Yasuharu / Imaoka, Tatsuhiko / Daino, Kazuhiro / Kakinuma, Shizuko / Nakajima, Tetsuo

    Anticancer research

    2023  Volume 43, Issue 6, Page(s) 2551–2559

    Abstract: Background/aim: Arsenite is a radiosensitizer of glioma cells both in vitro and in vivo; however, the underlying mechanism of action is unclear. Radiosensitizers specific for p53-deficient tumors are a promising adjunct to radiotherapy because, unlike ... ...

    Abstract Background/aim: Arsenite is a radiosensitizer of glioma cells both in vitro and in vivo; however, the underlying mechanism of action is unclear. Radiosensitizers specific for p53-deficient tumors are a promising adjunct to radiotherapy because, unlike normal cells, many tumor cells lack p53. Previously, we demonstrated that arsenite sensitizes the p53-deficient glioma cell line U87MG-E6 to X-rays.
    Materials and methods: Using flowcytometry, we expand these findings to p53-proficient U87MG cells exposed to heavy ion beams, including carbon and iron ions.
    Results: Arsenite sensitized U87MG-E6, but not U87MG, cells to heavy ion beams and X-rays. Cell cycle analysis indicated that sensitization of U87MG-E6 was related to an increase in the percentage of cells in the late S/G
    Conclusion: Arsenite sensitizes cells by increasing the percentage of cells in the late S/G
    MeSH term(s) Humans ; Arsenites/pharmacology ; Carbon ; Carmustine ; Cell Line, Tumor ; Cell Survival ; Glioma/pathology ; Tumor Suppressor Protein p53/metabolism
    Chemical Substances arsenite (N5509X556J) ; Arsenites ; Carbon (7440-44-0) ; Carmustine (U68WG3173Y) ; Tumor Suppressor Protein p53
    Language English
    Publishing date 2023-05-27
    Publishing country Greece
    Document type Journal Article
    ZDB-ID 604549-2
    ISSN 1791-7530 ; 0250-7005
    ISSN (online) 1791-7530
    ISSN 0250-7005
    DOI 10.21873/anticanres.16422
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  3. Article ; Online: Combined effects of radiation and simulated microgravity on intestinal tumorigenesis in C3B6F1 Apc

    Suzuki, Kenshi / Tsuruoka, Chizuru / Morioka, Takamitsu / Seo, Hitomi / Ogawa, Mari / Kambe, Ryosuke / Imaoka, Tatsuhiko / Kakinuma, Shizuko / Takahashi, Akihisa

    Life sciences in space research

    2024  Volume 41, Page(s) 202–209

    Abstract: Explorations of the Moon and Mars are planned as future manned space missions, during which humans will be exposed to both radiation and microgravity. We do not, however, know the health effects for such combined exposures. In a ground-based experiment, ... ...

    Abstract Explorations of the Moon and Mars are planned as future manned space missions, during which humans will be exposed to both radiation and microgravity. We do not, however, know the health effects for such combined exposures. In a ground-based experiment, we evaluated the combined effects of radiation and simulated microgravity on tumorigenesis by performing X-irradiation and tail suspension in C3B6F1 Apc
    MeSH term(s) Animals ; Mice ; Weightlessness Simulation ; Intestinal Neoplasms/pathology ; Intestinal Neoplasms/etiology ; Carcinogenesis/radiation effects ; Mice, Inbred C57BL ; Hindlimb Suspension ; Male ; X-Rays ; Disease Models, Animal ; Female ; Intestine, Small/radiation effects ; Intestine, Small/pathology ; Thymus Gland/radiation effects ; Thymus Gland/pathology ; Neoplasms, Radiation-Induced/pathology ; Neoplasms, Radiation-Induced/etiology
    Language English
    Publishing date 2024-03-30
    Publishing country Netherlands
    Document type Journal Article
    ISSN 2214-5532
    ISSN (online) 2214-5532
    DOI 10.1016/j.lssr.2024.03.005
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Ionizing radiation promotes, whereas calorie restriction suppresses, NASH and hepatocellular carcinoma in mice.

    Shang, Yi / Morioka, Takamitsu / Daino, Kazuhiro / Nakayama, Takafumi / Nishimura, Mayumi / Kakinuma, Shizuko

    International journal of cancer

    2023  Volume 153, Issue 8, Page(s) 1529–1542

    Abstract: The pathological conditions of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NASH) are the major risk factors for hepatocellular carcinoma (HCC). Exposure to DNA-damaging agents such as ionizing radiation is another risk factor for ... ...

    Abstract The pathological conditions of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NASH) are the major risk factors for hepatocellular carcinoma (HCC). Exposure to DNA-damaging agents such as ionizing radiation is another risk factor for HCC; calorie restriction (CR), however, effectively delays the onset of radiation-induced HCC. We investigated whether NASH is relevant to radiation-induced HCC and the cancer-preventing effect of CR. Eight-day-old male B6C3F1 mice were irradiated with 3.8 Gy of X-rays and then fed a standard diet or 30% CR diet from 49 days of age until necropsy, which was performed from 56 to 600 days with ~100-day intervals to assess both pathological changes and gene expression levels. We found that early-life exposure to radiation accelerated lipid accumulation and NASH-like histopathological changes in the liver, accompanied by accelerated development of HCC. CR ameliorated the changes in lipid metabolism in the liver and reversed the NASH-like pathology, which effectively delayed HCC development. Gene-expression profiling revealed the radiation-related activation and CR-related suppression of the peroxisome proliferator-activated receptor gamma/Cd36 pathway of transmembrane fatty-acid translocation before development of the NASH-like state. Thus, early-life exposure to radiation affects lipid metabolism and induces a steatoinflammatory microenvironment that favors HCC development. Therefore, targeting this pathway by CR (or measures that mimic CR) may be a promising strategy for preventing HCC caused by either radiation or other DNA-damaging agents.
    MeSH term(s) Male ; Animals ; Mice ; Carcinoma, Hepatocellular/pathology ; Non-alcoholic Fatty Liver Disease/complications ; Liver Neoplasms/genetics ; Caloric Restriction ; Liver/pathology ; Radiation, Ionizing ; Tumor Microenvironment
    Language English
    Publishing date 2023-07-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218257-9
    ISSN 1097-0215 ; 0020-7136
    ISSN (online) 1097-0215
    ISSN 0020-7136
    DOI 10.1002/ijc.34651
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  5. Article: [Radiation-induced brain cancer].

    Tsuruoka, Chizuru / Shimada, Yoshiya / Kakinuma, Shizuko

    Nihon rinsho. Japanese journal of clinical medicine

    2019  Volume 74 Suppl 7, Page(s) 77–82

    MeSH term(s) Brain Neoplasms ; Humans ; Neoplasms, Radiation-Induced
    Language Japanese
    Publishing date 2019-01-08
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 390903-7
    ISSN 0047-1852
    ISSN 0047-1852
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  6. Article ; Online: Impacts of psychological stress on high dose-rate radiation acute effects in a mouse experimental model.

    Nakajima, Tetsuo / Ninomiya, Yasuharu / Unno, Keiko / Morioka, Takamitsu / Nishimura, Mayumi / Kakinuma, Shizuko

    Journal of radiation research

    2022  Volume 63, Issue 4, Page(s) 602–608

    Abstract: Psychological stress affects health. Radiation workers in the medical field or astronauts living in space have possible risks of exposure to radiation, and psychological stress is considered to be easily induced in them due to activities performed in ... ...

    Abstract Psychological stress affects health. Radiation workers in the medical field or astronauts living in space have possible risks of exposure to radiation, and psychological stress is considered to be easily induced in them due to activities performed in small areas or stress conditions. The impact of psychological stress on the effects of radiation was evaluated in senescence-accelerated mouse prone 10 (SAMP10) mice and ddY mice using a confrontational housing model, which makes dominant and subordinate mice in a cage live together without severe quarrel. Mice of ddY and SAMP10 have been previously demonstrated to be influenced in terms of acute and late effects, respectively, under psychological stress by this model. In SAMP10 mice, irradiation with 4 Gy induced the death of irradiated mice under psychological stress. In ddY mice, irradiation with 5 Gy X-rays alone had almost no effect on the mouse survival, but irradiation in conditions of psychological stress promoted acute death of irradiated mice. In addition, hypocellular bone marrow was also observed histopathologically in irradiated ddY mice under stress. Psychological stress may promote damage caused by radiation through modulation of radio-sensitivity in bone marrow in mice. This model would be useful for evaluation of modulation of radiation-induced various effects by psychological stress.
    MeSH term(s) Animals ; Bone Marrow/radiation effects ; Dose-Response Relationship, Radiation ; Mice ; Mice, Inbred C57BL ; Models, Theoretical ; Radiation Injuries ; Stress, Psychological/complications ; X-Rays
    Language English
    Publishing date 2022-06-20
    Publishing country England
    Document type Journal Article
    ZDB-ID 603983-2
    ISSN 1349-9157 ; 0449-3060
    ISSN (online) 1349-9157
    ISSN 0449-3060
    DOI 10.1093/jrr/rrac028
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  7. Article ; Online: Molecular and cellular basis of the dose-rate-dependent adverse effects of radiation exposure in animal models. Part I: Mammary gland and digestive tract.

    Suzuki, Keiji / Imaoka, Tatsuhiko / Tomita, Masanori / Sasatani, Megumi / Doi, Kazutaka / Tanaka, Satoshi / Kai, Michiaki / Yamada, Yutaka / Kakinuma, Shizuko

    Journal of radiation research

    2023  Volume 64, Issue 2, Page(s) 210–227

    Abstract: While epidemiological data are available for the dose and dose-rate effectiveness factor (DDREF) for human populations, animal models have contributed significantly to providing quantitative data with mechanistic insights. The aim of the current review ... ...

    Abstract While epidemiological data are available for the dose and dose-rate effectiveness factor (DDREF) for human populations, animal models have contributed significantly to providing quantitative data with mechanistic insights. The aim of the current review is to compile both the in vitro experiments with reference to the dose-rate effects of DNA damage and repair, and the animal studies, specific to rodents, with reference to the dose-rate effects of cancer development. In particular, the review focuses especially on the results pertaining to underlying biological mechanisms and discusses their possible involvement in the process of radiation-induced carcinogenesis. Because the concept of adverse outcome pathway (AOP) together with the key events has been considered as a clue to estimate radiation risks at low doses and low dose-rates, the review scrutinized the dose-rate dependency of the key events related to carcinogenesis, which enables us to unify the underlying critical mechanisms to establish a connection between animal experimental studies with human epidemiological studies.
    MeSH term(s) Animals ; Humans ; Dose-Response Relationship, Radiation ; Neoplasms, Radiation-Induced/etiology ; Mammary Glands, Human ; Risk Assessment/methods ; Radiation Exposure/adverse effects ; Carcinogenesis ; Models, Animal ; Gastrointestinal Tract
    Language English
    Publishing date 2023-02-10
    Publishing country England
    Document type Review ; Journal Article
    ZDB-ID 603983-2
    ISSN 1349-9157 ; 0449-3060
    ISSN (online) 1349-9157
    ISSN 0449-3060
    DOI 10.1093/jrr/rrad002
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  8. Article ; Online: Molecular and cellular basis of the dose-rate-dependent adverse effects of radiation exposure in animal models. Part II: Hematopoietic system, lung and liver.

    Suzuki, Keiji / Imaoka, Tatsuhiko / Tomita, Masanori / Sasatani, Megumi / Doi, Kazutaka / Tanaka, Satoshi / Kai, Michiaki / Yamada, Yutaka / Kakinuma, Shizuko

    Journal of radiation research

    2023  Volume 64, Issue 2, Page(s) 228–249

    Abstract: While epidemiological data have greatly contributed to the estimation of the dose and dose-rate effectiveness factor (DDREF) for human populations, studies using animal models have made significant contributions to provide quantitative data with ... ...

    Abstract While epidemiological data have greatly contributed to the estimation of the dose and dose-rate effectiveness factor (DDREF) for human populations, studies using animal models have made significant contributions to provide quantitative data with mechanistic insights. The current article aims at compiling the animal studies, specific to rodents, with reference to the dose-rate effects of cancer development. This review focuses specifically on the results that explain the biological mechanisms underlying dose-rate effects and their potential involvement in radiation-induced carcinogenic processes. Since the adverse outcome pathway (AOP) concept together with the key events holds promise for improving the estimation of radiation risk at low doses and low dose-rates, the review intends to scrutinize dose-rate dependency of the key events in animal models and to consider novel key events involved in the dose-rate effects, which enables identification of important underlying mechanisms for linking animal experimental and human epidemiological studies in a unified manner.
    MeSH term(s) Animals ; Humans ; Radiation Dosage ; Neoplasms, Radiation-Induced ; Risk Assessment/methods ; Radiation Exposure/adverse effects ; Models, Animal ; Liver ; Lung ; Hematopoietic System ; Dose-Response Relationship, Radiation
    Language English
    Publishing date 2023-01-13
    Publishing country England
    Document type Review ; Journal Article
    ZDB-ID 603983-2
    ISSN 1349-9157 ; 0449-3060
    ISSN (online) 1349-9157
    ISSN 0449-3060
    DOI 10.1093/jrr/rrad003
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  9. Article ; Online: Corrigendum to "Azithromycin induces read-through of the nonsense Apc allele and prevents intestinal tumorigenesis in C3B6F1 Apc

    Semba, Ryoko / Morioka, Takamitsu / Yanagihara, Hiromi / Suzuki, Kenshi / Tachibana, Hirotaka / Hamoya, Takahiro / Horimoto, Yoshiya / Imaoka, Tatsuhiko / Saito, Mitsue / Kakinuma, Shizuko / Arai, Masami

    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

    2023  Volume 165, Page(s) 115082

    Language English
    Publishing date 2023-06-28
    Publishing country France
    Document type Published Erratum
    ZDB-ID 392415-4
    ISSN 1950-6007 ; 0753-3322 ; 0300-0893
    ISSN (online) 1950-6007
    ISSN 0753-3322 ; 0300-0893
    DOI 10.1016/j.biopha.2023.115082
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  10. Article ; Online: Rev1 overexpression accelerates N-methyl-N-nitrosourea (MNU)-induced thymic lymphoma by increasing mutagenesis.

    Sasatani, Megumi / Xi, Yang / Daino, Kazuhiro / Ishikawa, Atsuko / Masuda, Yuji / Kajimura, Junko / Piao, Jinlian / Zaharieva, Elena Karamfilova / Honda, Hiroaki / Zhou, Guanyu / Hamasaki, Kanya / Kusunoki, Yoichiro / Shimura, Tsutomu / Kakinuma, Shizuko / Shimada, Yoshiya / Doi, Kazutaka / Ishikawa-Fujiwara, Tomoko / Sotomaru, Yusuke / Kamiya, Kenji

    Cancer science

    2024  

    Abstract: Rev1 has two important functions in the translesion synthesis pathway, including dCMP transferase activity, and acts as a scaffolding protein for other polymerases involved in translesion synthesis. However, the role of Rev1 in mutagenesis and ... ...

    Abstract Rev1 has two important functions in the translesion synthesis pathway, including dCMP transferase activity, and acts as a scaffolding protein for other polymerases involved in translesion synthesis. However, the role of Rev1 in mutagenesis and tumorigenesis in vivo remains unclear. We previously generated Rev1-overexpressing (Rev1-Tg) mice and reported that they exhibited a significantly increased incidence of intestinal adenoma and thymic lymphoma (TL) after N-methyl-N-nitrosourea (MNU) treatment. In this study, we investigated mutagenesis of MNU-induced TL tumorigenesis in wild-type (WT) and Rev1-Tg mice using diverse approaches, including whole-exome sequencing (WES). In Rev1-Tg TLs, the mutation frequency was higher than that in WT TL in most cases. However, no difference in the number of nonsynonymous mutations in the Catalogue of Somatic Mutations in Cancer (COSMIC) genes was observed, and mutations involved in Notch1 and MAPK signaling were similarly detected in both TLs. Mutational signature analysis of WT and Rev1-Tg TLs revealed cosine similarity with COSMIC mutational SBS5 (aging-related) and SBS11 (alkylation-related). Interestingly, the total number of mutations, but not the genotypes of WT and Rev1-Tg, was positively correlated with the relative contribution of SBS5 in individual TLs, suggesting that genetic instability could be accelerated in Rev1-Tg TLs. Finally, we demonstrated that preleukemic cells could be detected earlier in Rev1-Tg mice than in WT mice, following MNU treatment. In conclusion, Rev1 overexpression accelerates mutagenesis and increases the incidence of MNU-induced TL by shortening the latency period, which may be associated with more frequent DNA damage-induced genetic instability.
    Language English
    Publishing date 2024-04-04
    Publishing country England
    Document type Journal Article
    ZDB-ID 2115647-5
    ISSN 1349-7006 ; 1349-7006
    ISSN (online) 1349-7006
    ISSN 1349-7006
    DOI 10.1111/cas.16159
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