Pall Martin L
Rev Environ Health. 2015;30(2):99-116. doi: 10.1515/reveh-2015-0001.
This review considers a paradigm shift on microwave electromagnetic field (EMF) action from only thermal effects to action via voltage-gated calcium channel (VGCC) activation. Microwave/lower frequency EMFs were shown in two dozen studies to act via VGCC activation because all effects studied were blocked by calcium channel blockers. This mode of action was further supported by hundreds of studies showing microwave changes in calcium fluxes and intracellular calcium [Ca2+]i signaling. The biophysical properties of VGCCs/similar channels make them particularly sensitive to low intensity, non-thermal EMF exposures. Non-thermal studies have shown that in most cases pulsed fields are more active than are non-pulsed fields and that exposures within certain intensity windows have much large biological effects than do either lower or higher intensity exposures; these are both consistent with a VGCC role but inconsistent with only a heating/thermal role. Downstream effects of VGCC activation include calcium signaling, elevated nitric oxide (NO), NO signaling, peroxynitrite, free radical formation, and oxidative stress. Downstream effects explain repeatedly reported biological responses to non-thermal exposures: oxidative stress; single and double strand breaks in cellular DNA; cancer; male and female infertility; lowered melatonin/sleep disruption; cardiac changes including tachycardia, arrhythmia, and sudden cardiac death; diverse neuropsychiatric effects including depression; and therapeutic effects. Non-VGCC non-thermal mechanisms may occur, but none have been shown to have effects in mammals. Biologically relevant safety standards can be developed through studies of cell lines/cell cultures with high levels of different VGCCs, measuring their responses to different EMF exposures. The 2014 Canadian Report by a panel of experts only recognizes thermal effects regarding safety standards for non-ionizing radiation exposures. Its position is therefore contradicted by each of the observations above. The Report is assessed here in several ways including through Karl Popper's assessment of strength of evidence. Popper argues that the strongest type of evidence is evidence that falsifies a theory; second strongest is a test of "risky prediction"; the weakest confirms a prediction that the theory could be correct but in no way rules out alternative theories. All of the evidence supporting the Report's conclusion that only thermal effects need be considered are of the weakest type, confirming prediction but not ruling out alternatives. In contrast, there are thousands of studies apparently falsifying their position. The Report argues that there are no biophysically viable mechanisms for non-thermal effects (shown to be false, see above). It claims that there are many "inconsistencies" in the literature causing them to throw out large numbers of studies; however, the one area where it apparently documents this claim, that of genotoxicity, shows no inconsistencies; rather it shows that various cell types, fields and end points produce different responses, as should be expected. The Report claims that cataract formation is produced by thermal effects but ignores studies falsifying this claim and also studies showing [Ca2+]i and VGCC roles. It is time for a paradigm shift away from only thermal effects toward VGCC activation and consequent downstream effects.
本综述探讨了微波电磁场(EMF)作用的范式转变,即从仅产生热效应转变为通过电压门控钙通道(VGCC)激活发挥作用。二十多项研究表明,微波/低频EMF通过VGCC激活发挥作用,因为所有研究的效应都被钙通道阻滞剂阻断。数百项研究显示微波会改变钙通量和细胞内钙[Ca2+]i信号,进一步支持了这种作用模式。VGCCs/类似通道的生物物理特性使其对低强度、非热EMF暴露特别敏感。非热研究表明,在大多数情况下,脉冲场比非脉冲场更具活性,并且在特定强度范围内的暴露比更低或更高强度的暴露具有更大的生物学效应;这些都与VGCC的作用一致,但与仅起加热/热作用不一致。VGCC激活的下游效应包括钙信号传导、一氧化氮(NO)升高、NO信号传导、过氧亚硝酸盐、自由基形成和氧化应激。下游效应解释了反复报道的对非热暴露的生物学反应:氧化应激;细胞DNA的单链和双链断裂;癌症;男性和女性不育;褪黑素降低/睡眠中断;心脏变化,包括心动过速、心律失常和心源性猝死;多种神经精神效应,包括抑郁症;以及治疗效果。可能存在非VGCC非热机制,但尚未证明其对哺乳动物有影响。通过对具有高水平不同VGCCs的细胞系/细胞培养物进行研究,测量它们对不同EMF暴露的反应,可以制定生物相关的安全标准。2014年加拿大一个专家小组的报告在非电离辐射暴露安全标准方面仅认可热效应。因此,其立场与上述各项观察结果均相矛盾。本文从多个方面对该报告进行了评估,包括通过卡尔·波普尔对证据强度的评估。波普尔认为,最强有力的证据类型是能证伪一种理论的证据;第二有力的是对“风险预测”的检验;最薄弱的是证实理论可能正确但绝不排除其他理论的预测。所有支持该报告结论即仅需考虑热效应的证据都是最薄弱类型的,只是证实了预测但并未排除其他可能性。相比之下,有成千上万项研究显然证伪了他们的立场。该报告认为不存在非热效应的生物物理可行机制(已证明是错误的,见上文)。它声称文献中有许多“不一致之处”,导致他们摒弃了大量研究;然而,它明显记录这一说法的一个领域,即遗传毒性领域,并未显示出不一致;相反,它表明不同细胞类型、场和终点产生不同的反应,这是可以预期的。该报告声称白内障形成是由热效应引起的,但忽略了证伪这一说法的研究以及显示[Ca2+]i和VGCC作用的研究。现在是时候从仅考虑热效应转向VGCC激活及其随之而来的下游效应的范式转变了。