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Journal Articles

The Bystander cell-killing effect mediated by nitric oxide in normal human fibroblasts varies with irradiation dose but not with radiation quality

Yokota, Yuichiro; Funayama, Tomoo; Muto, Yasuko*; Ikeda, Hiroko; Kobayashi, Yasuhiko

International Journal of Radiation Biology, 91(5), p.383 - 388, 2015/05

 Times Cited Count:11 Percentile:64.26(Biology)

We investigated the dependence of the bystander cell-killing effect on radiation dose and quality, and related molecular mechanisms. Human fibroblasts were irradiated with $$gamma$$-rays or carbon ions and co-cultured with non-irradiated cells. Survival rates of non-irradiated cells decreased and nitrite concentrations in culture medium increased with increasing doses. Their dose responses were similar between $$gamma$$-rays and carbon ions. Treatment of the specific nitric oxide (NO) radical scavenger prevented reductions in survival rates of non-irradiated cells. Negative relationships were observed between survival rates and nitrite concentrations. From these results, it was concluded that the bystander cell-killing effect mediated by NO radicals in human fibroblasts depends on irradiation doses, but not on radiation quality. NO radical production appears to be an important determinant of $$gamma$$-ray- and carbon-ion-induced bystander effects.

Journal Articles

Ion-species dependent bystander mutagenic effect on ${it HPRT}$ locus in normal human fibroblasts induced by C-, Ne- and Ar-ion microbeams

Suzuki, Masao*; Funayama, Tomoo; Yokota, Yuichiro; Muto, Yasuko*; Suzuki, Michiyo; Ikeda, Hiroko; Hattori, Yuya; Kobayashi, Yasuhiko

JAEA-Review 2014-050, JAEA Takasaki Annual Report 2013, P. 78, 2015/03

We have been studying the radiation-quality dependent bystander cellular effects, such as cell killing, mutation induction and chromosomal damage, using heavy-ion microbeams with different ion species. This year we focused on the ion-species dependent bystander mutagenic effect on ${it HPRT}$ locus in normal human fibroblasts. The confluent culture were irradiated using a 256 (16$$times$$16)-cross-stripe method using C, Ne and Ar microbeam. Gene mutation on ${it HPRT}$ locus was detected with 6-thioguanine resistant clones. The mutation frequency in cells irradiated with C-ion microbeams was 6 times higher than that of non-irradiated control cells and of the sample treated with specific inhibitor of gap-junction cell-to-cell communication. On the other hand, no enhanced mutation frequencies were observed in cells irradiated with either Ne- or Ar-ion microbeams. There is clear evidence that the bystander mutagenic effect via gap-junction communication depends on radiation quality.

Oral presentation

Bystander cell-killing effect mediated by nitric oxide in normal human fibroblasts depends in part on irradiation dose but not on radiation quality

Yokota, Yuichiro; Funayama, Tomoo; Ikeda, Hiroko; Sakashita, Tetsuya; Suzuki, Michiyo; Kobayashi, Yasuhiko

no journal, , 

Here, we investigate bystander effect. Normal human fibroblast WI-38 cells were irradiated with carbon ions or $$gamma$$-rays. Irradiated cells and non-irradiated cells were co-cultured. The survival rates of bystander cells decreased with dose at lower than 0.5 Gy and bottomed out at around 80%. In addition, the survival rates of bystander cells were not significantly different between carbon ions and $$gamma$$-rays at the same doses. These indicated the bystander cell-killing effect depends on irradiation dose but not on radiation quality. c-PTIO, a specific scavenger of nitric oxides (NO), suppressed the reduction of survival rates of bystander cells, showing NO has an important role to induce the bystander effect. The concentrations of nitrite, an oxide of NO, were measured. There were negative relationships between the survival rates of bystander cells and the nitrite concentrations of the medium. NO released to the medium maybe an important factor related to the bystander effect.

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