Proceedings of the Japan Academy, Series B
Online ISSN : 1349-2896
Print ISSN : 0386-2208
ISSN-L : 0386-2208
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Original Articles
  • Aoi OKAWA, Takamitsu MORIOKA, Tatsuhiko IMAOKA, Shizuko KAKINUMA, Yosh ...
    2020 Volume 96 Issue 5 Pages 171-179
    Published: May 11, 2020
    Released: May 11, 2020
    JOURNALS FREE ACCESS FULL-TEXT HTML
    Supplementary material

    It is generally thought that younger people are more susceptible to cancer development after exposure to ionizing radiation in reference to epidemiological studies and animal experiments. However, little is known about the age-dependent alteration in DNA repair ability. In the present study, we examined the expression levels of proteins involved in the repair of DNA double-strand breaks through non-homologous end joining (NHEJ), i.e., DNA-dependent protein kinase catalytic subunit (DNA-PKcs), X-ray repair cross-complementing 4 (XRCC4) and XRCC4-like factor (XLF). We found that the expression of DNA-PKcs in brain tissues was higher in neonatal mice (1 week after birth) than in young adult mice (7 weeks after birth). In association with this, DNA double-strand breaks were repaired more rapidly in the brain tissues of neonatal mice than in those of young adult mice. The current results suggested a possible role for DNA-PKcs protecting developing brain tissues from DNA double-strand breaks.

  • Yukari TOTSUKA, Yuya MAESAKO, Hanako ONO, Momoko NAGAI, Mamoru KATO, M ...
    2020 Volume 96 Issue 5 Pages 180-187
    Published: May 11, 2020
    Released: May 11, 2020
    JOURNALS FREE ACCESS FULL-TEXT HTML
    Supplementary material

    1,4-Dioxane is a genotoxic carcinogen, and its mutagenic properties were recently observed in the liver of guanine phosphoribosyl transferase (gpt) delta transgenic rats. However, the mechanisms of its genotoxicity remain unclear. We analyzed DNA adduct formation in rat livers following 1,4-dioxane treatment. After administering 1,4-dioxane in drinking water at doses of 0, 20, 200, and 5,000 ppm, liver adduct formation was analyzed by DNA adductome analysis. Adducts in treated rat livers were dose-dependently increased compared with those in the control group. Principal component analysis-discriminant analysis (PCA-DA) clearly revealed two clusters of DNA adducts, associated with 0 ppm and low-dose (20 ppm) 1,4-dioxane-treatment versus middle- and high-dose (200, 5,000 ppm)-treated rats. After confirming the intensity of each adduct, three adducts were screened as characteristic of 1,4-dioxane treatment. Two of the three candidates contained thymine or cytidine/uracil moieties. Another candidate was identified as 8-oxo-dG based on mass fragmentation together with high-resolution accurate-mass (HRAM) mass spectrometry data. Oxidative stress responses may partly explain the mechanisms of increased mutations in the liver of gpt delta rats following 1,4-dioxane treatment.

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