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Journal Articles

Immunofluorescence observation of oxidative damage of DNA induced by heavy ions from TIARA

Kitabatake, Satomi*; Ushiroda, Tota*; Hirayama, Ryoichi*; Furusawa, Yoshiya*; Funayama, Tomoo; Yokota, Yuichiro; Okahata, Yoshio*; Ito, Atsushi*

JAEA-Review 2014-050, JAEA Takasaki Annual Report 2013, P. 86, 2015/03

Biological effects of high-LET radiation could be understood in terms of the ion track structure. Therefore the evaluation of the contribution of both core and penumbra regions to biological effects is an important issue for the study of high-LET effects. In the present study, we developed a protocol to make a uniform DNA sheet with insoluble nature in aqueous solution, and explored the applicability to the detection of 8-OHdG distributions after heavy-ion irradiation. Water-insoluble DNA sheet was irradiated with proton and neon ion beams at JAEA-Takasaki. After irradiation DNA samples were incubated with an 8-OHdG antibody followed by with a second antibody containing a fluorescence probe. The preliminary results indicated that upon ion irradiation randomly distributed dot-like fluorescence was observed, suggesting that these dots may be from incident ions.

Journal Articles

Nonhomologous end-joining repair plays a more important role than homologous recombination repair in defining radiosensitivity after exposure to high-LET radiation

Takahashi, Akihisa*; Kubo, Makoto*; Ma, H.*; Nakagawa, Akiko*; Yoshida, Yukari*; Isono, Mayu*; Kanai, Tatsuaki*; Ono, Tatsuya*; Furusawa, Yoshiya*; Funayama, Tomoo; et al.

Radiation Research, 182(3), p.338 - 344, 2014/09

 Times Cited Count:24 Percentile:12.87(Biology)

To clarify whether high-LET radiation inhibits all repair pathways or specifically one repair pathway, studies were designed to examine the effects of radiation with different LET values on DNA DSB repair and radiosensitivity. Embryonic fibroblasts bearing repair gene KO were exposed to X rays, carbon-, iron-, neon- and argon-ion beams. Cell survival was measured with colony-forming assays. The sensitization enhancement ratio (SER) values were calculated using the 10% survival dose of wild-type cells and repair-deficient cells. Cellular radiosensitivity was listed in descending order: double-KO cells $$>$$ NHEJ-KO cells $$>$$ HR-KO cells $$>$$ wild-type cells. Although HR-KO cells had an almost constant SER value, NHEJ-KO cells showed a high-SER value when compared to HR-KO cells, even with increasing LET values. These results suggest that with carbon-ion therapy, targeting NHEJ repair yields higher radiosensitivity than targeting homologous recombination repair.

Journal Articles

Effects of hydration on the induction of strand breaks, base lesions, and clustered damage in DNA films by $$alpha$$-radiation

Yokoya, Akinari; Cunniffe, S. M. T.*; Stevens, D. L.*; O'Neill, P.*

Journal of Physical Chemistry B, 107(3), p.832 - 837, 2003/01

 Times Cited Count:23 Percentile:44.16(Chemistry, Physical)

no abstracts in English

Oral presentation

Epigenetic modification potentially sensitizes heavy-ion therapy for malignancy

Saito, Katsuyo*; Funayama, Tomoo; Kobayashi, Yasuhiko; Murakami, Takashi*

no journal, , 

Malignant melanoma is one of the most common cutaneous malignancies. Epigenetic modifiers, such as histone deacetylase inhibitors (HDACi) and DNA methyltransferase inhibitors, have emerged recently as promising anticancer agents and has been expected as a sensitizer for other cancer therapeutics including radiotherapy. In addition, the biological effects of the high linear energy transfer (LET) heavy-ion radiation are more pronounced than the low-LET radiation. These accumulating evidences allowed us to investigate whether the use of HDACi could sensitize melanoma cells for the heavy-ion therapy. Treatment of B16F10 melanoma cells with HDACi in combination with heavy-ion radiation provided enhanced anti-tumor effects. These data suggest that combination of HDACi together with heavy-ion therapy may provide improved therapeutic responses in melanoma patients.

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