この研究は、超低周波磁界（ELF MF: 50Hz、1mT）にばく露したヒト神経芽腫細胞SH-SY5Yで観察された過剰増殖の背景として、メチルグリオキサール（MG）に対する防護の促進、およびエネルギー代謝経路の変更が起きているか否かを調べた。その結果、ELF MFはSH-SY5Y細胞株の増殖活性を増加させるだけでなく、MGへの防護を高めることを通して細胞防御メカニズムのトリガーを引くこと、それと併せて、細胞の速い成長を支えるために代謝エネルギー管理の効率を高めることが示された、と報告している。
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The effects of exposure of human neuroblastoma cells to a 50 Hz magnetic field should be investigated by means of cell proliferation, metabolism and cyto-protective mechanisms to research the role of extremely low frequency magnetic fields in tumor promotion.
In general, tumor cells depend on glycolysis for energy supply and show an increased glycolysis rate compared to normal cells. However, this also increases the production of methylglyoxal, which is a highly cytotoxic and cancer-static glycolytic by-product. Cancer cellular defense mechanisms against methylglyoxal are therefore regarded as a factor associated with tumor promotion. Therefore, in one test approach, 100 µM of methylglyoxal was added to the cells after exposure to the magnetic field and cell growth was investigated after 24 hours.
Several enzymes and biomolecules were investigated:
- Glyoxalases are the main enzymes for the degradation of methylglyoxal.
- Glutathione was investigated as reduced glutathione is an essential cofactor for the degradation of methylglyoxal.
- Argpyrimidine was used as a marker of specific methylglyoxal dependent protein damage.
- GAPDH was measured as it is suggested that it might modify the intracellular methylglyoxal levels.
- The citrate synthase enzyme activity is a marker for mitochondrial activity and PGC-1α is a marker for mitochondrial biogenesis.
- The phosphofructo-kinase is a key enzyme for glycolysis.
- βIII-tubulin was used as a marker for cell differentiation.
All tests were replicated 3-5 times.
|ばく露時間||continuous for 5, 10 or 15 days|
|ばく露装置の詳細||solenoids were placed in incubators and produced a highly homogeneous field; temperature in the cell culture was controlled with accuracy better than 0.05°C and no magnetic field-induced heating was observed|
|Sham exposure||A sham exposure was conducted.|
|Additional information||simultaneous exposure and sham exposure in randomly chosen energized and non-energized solenoids|
Exposure to the magnetic field led to a significantly increased cell proliferation after 5-15 days accompanied by a significantly reduced cell differentiation (decrease of βIII-tubulin), indicating a more aggressive tumor growth compared to sham exposure.
After 5 days, the glycolysis and the sensitivity to exogenous methylglyoxal were significantly increased in exposed cells compared to sham exposure. After 15 days, however, an increase in the protective mechanisms against methylglyoxal by means of a significant increase in the quantity and enzyme activity of glyoxalase 2 and the amounts of GAPDH and reduced glutathione was measured in exposed cells compared to sham exposed cells. The resistance of exposed cells to exogenous methylglyoxal was significantly increased after 15 days. In addition, the production of methylglyoxal was reduced by a significant reduction of glycolysis in exposed cells compared to sham-exposed cells, and the mitochondrial activity was significantly increased, presumably to compensate the reduced glycolysis and to support the increased proliferation. The authors pointed out that an increased mitochondrial activity is also associated with a more aggressive tumor growth.
The authors conclude that exposure to a 50 Hz magnetic field could enhance tumor promotion by increasing cell proliferation, enhancing cell-protective mechanisms and establishing a more efficient energy metabolism in human neuroblastoma cells. These changes seemed to be an adaptation process, which was only completed after 15 days of exposure. After 5 days of exposure, a sensitive transition state seemed to be reached.