射频电磁场和低剂量化学毒物复合暴露致MEF细胞遗传毒性及机制研究

移动电话辐射等暴露的可能健康危害备受争议，其关键是低强度射频电磁场作用引发生物学效应的作用机理不清楚。我们的前期研究发现射频电磁场和低剂量化学毒物诱导小鼠胚胎成纤维细胞（MEF）DNA损伤及修复的动态变化，但均未能造成细胞损伤；射频电磁场和低剂量化学毒物复合暴露导致细胞损伤。为深入研究其生物学机制，本项目以野生型和DNA损伤修复基因（Atm，p53，Xrcc1）缺陷型MEF细胞为模型，以代表性环境化学毒物（H2O2、4NQO、 Cd2+、Cr6+）和射频电磁场复合暴露为研究对象，分析复合暴露条件下射频电磁场暴露的阈值，探索阐明细胞感受特定复合暴露后产生的DNA损伤及修复机制，提出复合暴露加剧DNA损伤的生物物理学基础。项目研究预期明确射频电磁场与低剂量化学毒物交互作用致细胞损伤的分子基础，研究成果有助于探索阐明射频电磁场作用的生物物理机制，为环境电磁场健康风险评估提供实验证据和理论。

Public concerns have been raised on the potential health hazard of exposure to increasing environmental radiofrequency electromagnetic fields (RF-EMF), which are mainly emitted from mobile phones, base stations, Wi-fi, etc. However, the possibility of biological and health effects of exposure to RF-EMF remains controversial and their biophysical mechanisms are largely unknown. Therefore, it is critical to elucidate the mechanism of cellular response to RF-EMF exposure. To address the debate on whether RF-EMFs are genotoxic, we compared the effects of RF-EMF exposure on genomic DNA in mouse embryonic fibroblasts (MEFs) with proficient (Atm+/+) or deficient (Atm−/−) Atm. Interestingly, RF-EMF exposure induced changeable DNA damage response and the Atm deficiency increase the sensitivity of MEF cells to RF-EMF exposure, however, these DNA damage responses did not result in abnormal cellular behaviors. Similar phenomena was found when the cells were treated by low-dose chemical toxicants (e.g., H2O2 and 4NQO). Importantly, the cell viability was significantly inhibited when the Atm+/+ MEF cells were co-exposed to low-dose H2O2 and 4NQO, suggesting exposure either low-dose chemical toxicant may enhance the sensitivity of the cells to the other one. We also found the co-exposure of RF-EMF and low-dose H2O2 inhibited cell viability of Atm+/+ MEF cells. These finding drive us to further explore the mechanisms on co-exposure to RF-EMF and low-dose chemical toxicants on DNA damage. In this project, we will 1) confirm the DNA damage effect on MEF cells by co-exposure to RF-EMF and different chemical toxicant (e.g., H2O2, 4NQO Cd2+, Cr6+). and determine the threshold of RF-EMF under different co-exposure conditions; 2) compare the cellular response to aforementioned co-exposure in the MEF cell lines lacking different gene related to DNA damage repair (Atm, p53, Xrcc1) and determine sensitive DNA damage repair pathways to RF-EMF under the co-exposure; 3) investigate the specific role of interaction between RF-EMF and low-dose chemical toxicants in aggravation of DNA damage, and how does RF-EMF and each low-dose chemical toxicant contribute to the event and what are the targets (anti-oxidants or DNA damage repair factors); 4) examine if RF-EMF exposure in vitro affect the physical characteristics of the anti-oxidants or DNA damage repair factors, and if co-exposure to RF-EMF and low-dose chemical toxicant enhance voluntary of the anti-oxidants or DNA damage repair factors. We expect this study to determine the DNA damage repair pathway responding to co-exposure by RF-EMF and low-dose chemical toxicants, and to uncover the roles of key anti-oxidants or DNA damage repair factors that are sensitive to the co-exposure. Our study will shed on the biophysical mechanisms of RF-EMF acting on organism, and provide both experimental evidence and theory supports for future health risk assessment of environmental RF-EMF exposure.