この研究は、MCF-7細胞およびSH-SY5Y細胞への 50Hz磁界(0.25および0.5mT)の単独ばく露およびシスプラチン(CDDP)との共ばく露が、DNA修復経路に関与する7つの遺伝子(GADD45A、XRCC1、XRCC4、Ku70、Ku80、DNA-PKcs、LIG4)のmRNAレベルに与える影響を調べた。50Hz磁界のばく露パターンは3通り(5分ON/5分OFF、15分ON/15分OFF、30分ON継続)とした。mRNAレベルを定量的実時間PCR法で測定した。その結果、MCF-7細胞への磁界ばく露(0.5mT、15分ON/15分OFF)によりGADD45A、XRCC1、XRCC4、Ku80、Ku70、LIG4でmRNAレベルの低下が見られ、上昇した遺伝子はなかった;MCF-7およびSH-SY5Y細胞において、CDDP単独ばく露に比べ、CDDP+EMF共ばく露においてCDDPの50%阻害濃度が有意に増加した;MCF-7およびSH-SY5Y細胞での共ばく露において、GADD45AのmRNAレベルは上昇したが、XRCC4、Ku80、Ku70、DNA-PKcsのmRNAレベルは低下した、と報告している。
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The effects of co-exposure of two cancer cell lines to different 50 Hz magnetic fields and cisplatin on gene expression of genes involved in DNA repair should be investigated in view of a possible therapeutic use.
Two 50 Hz magnetic flux densities (0.25 and 0.50 mT), three exposure patterns (5 min field "on"/5 min field "off", 15 min field "on"/15 min field "off", continuously 30 min field "on") and two cell lines (MCF-7 and SHSY5Y) were used.
To test whether exposure to the magnetic field might sensitize cells to cisplatin, several groups were also tested in a co-exposure with cisplatin (15 µg/ml for MCF-7 cells, 4 µg/m for SH-SY5Y cells). To test whether co-exposure to the magnetic field and cisplatin might sensitize cells to double-strand breaks from, e.g., irradiation therapy, some co-exposed cells were treated with 1 µg/ml bleomycin, an irradiation mimicking drug.
ばく露 | パラメータ |
---|---|
ばく露1:
50 Hz
ばく露時間:
intermittent 5 min field "on"/5 min field "off" for 30 minutes
MCF-7 cells
|
|
ばく露2:
50 Hz
ばく露時間:
intermittent 15 min field "on"/15 min field "off" for 30 minutes
MCF-7 cells
|
|
ばく露3:
50 Hz
ばく露時間:
continuous for 30 minutes
MCF-7 cells
|
|
ばく露4:
50 Hz
ばく露時間:
intermittent 5 min field "on"/5 min field "off" for 30 minutes
MCF-7 cells
|
|
ばく露5:
50 Hz
ばく露時間:
intermittent 15 min field "on"/15 min field "off" for 30 minutes
MCF-7 cells, SH-SY5Y cells, partially with cisplatin and bleomycin
|
|
ばく露6:
50 Hz
ばく露時間:
continuous for 30 minutes
MCF-7 cells
|
|
周波数 | 50 Hz |
---|---|
タイプ |
|
ばく露時間 | intermittent 5 min field "on"/5 min field "off" for 30 minutes |
Additional information | MCF-7 cells |
測定量 | 値 | 種別 | Method | Mass | 備考 |
---|---|---|---|---|---|
磁束密度 | 0.25 mT | - | - | - | - |
周波数 | 50 Hz |
---|---|
タイプ |
|
ばく露時間 | intermittent 15 min field "on"/15 min field "off" for 30 minutes |
Additional information | MCF-7 cells |
ばく露の発生源/構造 |
|
---|
測定量 | 値 | 種別 | Method | Mass | 備考 |
---|---|---|---|---|---|
磁束密度 | 0.25 mT | - | - | - | - |
周波数 | 50 Hz |
---|---|
タイプ |
|
ばく露時間 | continuous for 30 minutes |
Additional information | MCF-7 cells |
ばく露の発生源/構造 |
|
---|
測定量 | 値 | 種別 | Method | Mass | 備考 |
---|---|---|---|---|---|
磁束密度 | 0.25 mT | - | - | - | - |
周波数 | 50 Hz |
---|---|
タイプ |
|
ばく露時間 | intermittent 5 min field "on"/5 min field "off" for 30 minutes |
Additional information | MCF-7 cells |
ばく露の発生源/構造 |
|
---|
測定量 | 値 | 種別 | Method | Mass | 備考 |
---|---|---|---|---|---|
磁束密度 | 0.5 mT | - | - | - | - |
周波数 | 50 Hz |
---|---|
タイプ |
|
ばく露時間 | intermittent 15 min field "on"/15 min field "off" for 30 minutes |
Additional information | MCF-7 cells, SH-SY5Y cells, partially with cisplatin and bleomycin |
ばく露の発生源/構造 |
|
---|
測定量 | 値 | 種別 | Method | Mass | 備考 |
---|---|---|---|---|---|
磁束密度 | 0.5 mT | - | - | - | - |
周波数 | 50 Hz |
---|---|
タイプ |
|
ばく露時間 | continuous for 30 minutes |
Additional information | MCF-7 cells |
ばく露の発生源/構造 |
|
---|
測定量 | 値 | 種別 | Method | Mass | 備考 |
---|---|---|---|---|---|
磁束密度 | 0.5 mT | - | - | - | - |
A general trend towards a down-regulation of DNA repair involved genes was found in exposed cells compared to sham exposed cells. Intermittent exposure of field 5 (15 min field "on"/15 min field "off" with 0.5 mT) showed the most distinct results with significantly downregulated genes (GADD45A, XRCC1, XRCC4, Ku80, Ku70 and LIG4).
A significant elevation of the IC50 was found in cells co-exposed to the magnetic field and cisplatin (field 5) compared to a cisplatin treatment alone, indicating that magnetic field exposure did not sensitize cells to cisplatin.
However, co-exposure to the magnetic field and cisplatin significantly decreased the gene expressions of XRCC4, Ku80, Ku70 and DNA-PKcs (field 5) compared to sham exposed cells, while the gene expression of GADD45A was significantly downregulated. This was not observed in cells exposed to cisplatin alone. Cell viability was significantly reduced in a co-exposure to the magnetic field, cisplatin and bleomycin compared to a treatment with cisplatin and bleomycin alone, indicating that cells co-exposed to the magnetic field and cisplatin were sensitized to bleomycin.
The authors conclude that co-exposure to a 50 Hz magnetic field and cisplatin might downregulate genes involved in DNA repair, what could sensitize cancer cells to double-strand break-inducing drugs and irradiation therapy.
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