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Shikazono, Naoya; Akamatsu, Ken; Takahashi, Momoko*; Noguchi, Miho; Urushibara, Ayumi; O'Neill, P.*; Yokoya, Akinari
Mutation Research; Fundamental and Molecular Mechanisms of Mutagenesis, 749(1-2), p.9 - 15, 2013/09
Times Cited Count:12 Percentile:36.54(Biotechnology & Applied Microbiology)We examined the biological consequences of bi-stranded clustered damage sites, consisting of a combination of DNA lesions using a bacterial plasmid-based assay. The transformation efficiencies were significantly lower for the bi-stranded clustered GAP/AP lesions than for either a single GAP or a single AP site. When the two lesions were separated by 10-20 bp, the transformation efficiencies were comparable with those of the single lesions. This recovery of transformation efficiency for separated lesions requires DNA polymerase I (Pol I) activity. Analogously, the mutation frequency was enhanced in a bi-stranded cluster containing a GAP and an 8-oxoG, and Pol I was found to play an important role in minimising mutations induced as a result of clustered lesions. These results indicate that the biological consequences of clustered DNA damage strongly depend on Pol I activity.
Kawachi, Tetsuya; Kado, Masataka; Tanaka, Momoko; Hasegawa, Noboru; Nagashima, Keisuke; Sukegawa, Kota*; Lu, P.; Takahashi, Kenjiro; Namba, Shinichi; Koike, Masato; et al.
Applied Optics, 42(12), p.2198 - 2205, 2003/04
Times Cited Count:27 Percentile:72.16(Optics)no abstracts in English
Kawachi, Tetsuya; Kado, Masataka; Tanaka, Momoko; Sasaki, Akira; Hasegawa, Noboru; Kilpio, A.*; Namba, Shinichi; Nagashima, Keisuke; Lu, P.; Takahashi, Kenjiro; et al.
Physical Review A, 66(3), p.033815_1 - 033815_7, 2002/09
Times Cited Count:85 Percentile:93.00(Optics)A silver and tin slab targets were irradiated by a line-focused CPA glass laser light. In this experiment, the laser pulses consisted of two pulses with 4 ps duration, separated by 1.2 ns. Strong amplification in the nickel-like silver and tin x-ray lasers at the wavelengths of 13.9nm and 12.0nm was demonstrated with a pumping energy of 12 J and 14 J, respectively, and gain-saturation behaviors could be seen. A hydro-dynamics simulation coupled with a collisional-radiative model was performed under the present experimental condition, and the calculated result was compared with the experimental results.
Kado, Masataka; Kawachi, Tetsuya; Tanaka, Momoko; Hasegawa, Noboru; Takahashi, Kenjiro; Namba, Shinichi; Sukegawa, Kota*; Sasaki, Akira; Lu, P.; Tang, H.; et al.
Soft X-Ray Lasers and Applications IV (Proceedings of SPIE Vol.4505), p.54 - 61, 2001/12
Times Cited Count:4 Percentile:79.44(Optics)no abstracts in English
Takahashi, Momoko; Noguchi, Miho; Hirakawa, Hirokazu*; Okayasu, Ryuichi*
no journal, ,
Ionizing radiation has been widely used as a tool for tumor treatment. However, there are still difficulties to treat the solid tumor with only irradiation. Several studies have been shown that the combination therapy using both X-irradiation and antitumor drug is more effective to tumor compared with X-irradiation only. Previously Noguchi et al. showed the Hsp90 inhibitor 17AAG induced tumor cell death effectively with X-irradiation. Hsp90 is the enzymes activated by cellular stress and activates several tumor-related genes. To clarify whether or not the combination therapy of carbon ion beam and 17AAG is effective to solid tumors, we tested the growth of solid tumor with the combination of X-irradiation and 17AAG and compared the results from study.
Okayasu, Ryuichi*; Hirakawa, Hirokazu*; Noguchi, Miho; Yu, D.*; Takahashi, Momoko; Hirayama, Ryoichi*; Fujimori, Akira*
no journal, ,
17AAG, an Hsp90 inhibitor was shown to radiosensitize certain human tumor cells exposed to X-rays, while this sensitization was not clearly observed in normal human cells. The mechanism of this was suggested to come from inhibition of DNA double strand break (DSB) repair, particularly impairment of homologous recombination repair (HRR) pathway by this drug (Noguchi et al 2006). Key proteins associated with HRR seem to be affected by this inhibitor. To our surprise, tumor radiosensitization with 17AAG was also observed in cells exposed to high LET carbon ions (70 kev/um). Independently we also found that knockdown of BRCA2, a key HRR protein significantly radiosensitized human tumor cells. These results indicate that there seem to be a radio-sensitization mechanism associated with the combination of HRR inhibition and high LET radiation, and this may occur particularly in S-phase cells. Furthermore, we also used mouse xenograft model to examine the combined effect of 17AAG and high LET carbon irradiation. For this purpose, SQ5 human lung tumor cells were implanted on the leg of nude mice and the tumor growth was observed in the combined treatment as compared with radiation or drug treatment alone. Our preliminary results indicate that tumor growth was more inhibited in the 17AAG and carbon irradiation than carbon or 17AAG treatment alone. These data suggest that an effective tumor control might be obtained by combining an HRR inhibitor with high LET carbon irradiation.
Takahashi, Momoko; Shikazono, Naoya
no journal, ,
no abstracts in English
Takahashi, Momoko; Shikazono, Naoya
no journal, ,
no abstracts in English
Takahashi, Momoko; Shikazono, Naoya
no journal, ,
DNA is damaged by various factors and unrepaired DNA damage would cause alterations of the genome, and thus various biological effects. To avoid these effects, there are diverse mechanisms to repair DNA damage in cells. Clustered DNA damage, defined as two or more lesions in one to two helical turns of DNA, is induced by ionizing radiation. Clustered DNA damage is considered to be refractory to repair and therefore highly lethal and mutagenic. However, the mechanism on how clustered DNA damage causes mutagenesis or lethality is still largely unknown. We constructed lesion-containing plasmids using a novel approach in order to analyze repair of clustered DNA damage. The method introduced by Karata was modified to construct the plasmid. We found that the constructed plasmid DNA had a defined lesion. As DNA lesions could be placed at any position on either strand, the method allows us to construct cluster DNA damage in a plasmid, and would be highly useful in analyzing processing of clustered DNA damage. We will discuss about the analysis of repair of clustered DNA damage in , as an example.
Takahashi, Momoko*; Shikazono, Naoya
no journal, ,
Takahashi, Momoko; Shikazono, Naoya
no journal, ,