| アイテムタイプ |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2025-02-27 |
| タイトル |
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タイトル |
Human?Mouse Comparison of the Multistage Nature of Radiation Carcinogenesis in a Mathematical Model |
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言語 |
en |
| 言語 |
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言語 |
eng |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
| 著者 |
Imaoka Tatsuhiko
Tanaka Satoshi
Tomita Masanori
Doi Kazutaka
Sasatani Megumi
Suzuki Keiji
Yamada Yutaka
Kakinuma Shizuko
Kai Michiaki
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| 抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
Mouse models are vital for assessing risk from environmental carcinogens including ionizing radiation, yet the interspecies difference in the dose response precludes direct application of experimental evidence to humans. Herein, we take a mathematical approach to delineate the mechanism underlying the human?mouse difference in radiation-related cancer risk. We used a multistage carcinogenesis model assuming a mutational action of radiation to analyze previous data of cancer mortality in the Japanese atomic bomb survivors and in lifespan mouse experiments. Theoretically, the model predicted that exposure will chronologically shift the age-related increase in cancer risk forward by a period corresponding to the time in which the spontaneous mutational process generates the same mutational burden as that the exposure generates. This model appropriately fitted both human and mouse data and suggested a linear dose response for the time shift. The effect per dose decreased with increasing age at exposure similarly between humans and mice on a per-lifespan basis (0.72- and 0.71-fold, respectively, for every tenth lifetime). The time shift per dose was larger by two orders of magnitude in humans (7.8 and 0.046 y per Gy for humans and mice, respectively, when exposed at ~35% of their lifetime). The difference was mostly explained by the two orders of magnitude difference in spontaneous somatic mutation rates between the species plus the species-independent radiation-induced mutation rate. Thus, the findings delineate the mechanism underlying the interspecies difference in radiation-associated cancer mortality and may lead to the use of experimental evidence for risk prediction in humans. |
| 書誌情報 |
International Journal of Cancer
巻 155,
号 6,
p. 1101-1111,
発行日 2024-04
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| 出版者 |
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出版者 |
Wiley |
| ISSN |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
1097-0215 |
| PubMed番号 |
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識別子タイプ |
PMID |
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関連識別子 |
38688826 |
| DOI |
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識別子タイプ |
DOI |
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関連識別子 |
10.1002/ijc.34987 |
Submitted Version (no embargo).pdf (2.1 MB)
