Modulation of radical pairs dynamics immersed in an ELF-EMF: The effect on hepatocarcinogenesis

Abstract

The most suitable mechanism of action of electromagnetic fields (EMF) on biological systems is the effect on the radical pair (RP) recombination through the Zeeman effect and hyperfine interaction, which changes the rate of reactions or the product distribution. Enzyme reactions with RP intermediates can be altered by EMF, like those catalyzed by cytochrome P450 enzymes (CYP450), a heme-thiolate family protein that detoxifies xenobiotics and involved in chemical carcinogenesis. CYP450 activate chemical carcinogens producing an enormous amount of free radicals, which damage the DNA resulting in the malignant transformation of cells. During the activation, CYP450 produce spin-correlated RP intermediates that can either go to recombination or to continue the catalytic process. As CYP450 are electron carrier proteins, it is possible that RP intermediates may be affected by EMF. It was previously found that periodic treatment with extremely low frequency electromagnetic fields (ELF-EMF) inhibits more than 50% the number and area of preneoplastic lesions in rats with chemically induced hepatocarcinogenesis through reduction of cell proliferation. In this work, we developed a quantum mechanical model based on RP mechanism in order to explain the experimental effects of ELF-EMF on the free radicals produced in the early stages of chemical carcinogenesis.

Cytoprotective Effect of 120 Hz Electromagnetic Fields on Early Hepatocarcinogenesis: Experimental and Theoretical Findings

“…In our research group, we have implemented the use of an ELF-EMF to study hepatocarcinogenesis in its early stages to assess its cytoprotective effect, both experimentally and theoretically. We proposed that it is possible to deter the carcinogenic process induced by chemical carcinogens in the early stages during enzymatic procarcinogen activation by CYP450 through the modulation of charge migration in the electron transfer reactions involved in oxidation [8,9]. This has been achieved by modulating the magnetic sensitivity of short-lived RP intermediaries produced during the catalytic cycle using ELF-EMF.…”

“…In this chapter, we review the experimental and theoretical findings found by our research group within the context of the current knowledge on the cytoprotective effect of ELF-EMF in the early stages of OS induced by chemical carcinogenesis (ChemCar). We use the term cytoprotection because of the conferred protection that dissuades or modulates, controls, or deviates processes originated from bioactivation of procarcinogens, which avoids or diminishes damage to cells or its molecular components [8,9]. On the one hand, we describe and discuss the experimental findings of our group on the effect of daily treatment with 4.5 mT (120 Hz) of ELF-EMF.…”

“…The early stages of OS in rats with chemically induced hepatocarcinogenesis (ChemIndHep) employed the modified resistant hepatocyte model (MRHM) with Fischer rats 344 [10]. Otherwise, as the molecular mechanisms responsible for this effect are still unclear, we developed a quantum mechanical model based on the RPM and the Haberkorn approximation to explain the experimental effects of ELF-EMF on the free radicals produced in the early stages of ChemIndHep [8]. It is plausible to assume that, through the employment of RPM using ELF-EMF, we modulated the RP intermediates involved in free radical generation (as has been reported for other reactions [11]).…”

“…Then, directing them towards lower energetic states in such a way that the activation of oxidative products diminished, and the electrophile damage to cells is reduced [9]. Thanks to this multidisciplinary analysis, we can understand the carcinogenic chemical process based on the behavior of charged particles generated during the enzymatic activation of the procarcinogen, that is, when the DNA still has not yet been damaged in the early stages of carcinogenesis [8,9]. The results of this work allow us to advertise the basis for the design of tailored therapeutic strategies or clinical applications of ELF-EMF as a coadjutant in the treatment of several diseases related to oxidative damage as occurs in cancer [8,9].…”

“…Thanks to this multidisciplinary analysis, we can understand the carcinogenic chemical process based on the behavior of charged particles generated during the enzymatic activation of the procarcinogen, that is, when the DNA still has not yet been damaged in the early stages of carcinogenesis [8,9]. The results of this work allow us to advertise the basis for the design of tailored therapeutic strategies or clinical applications of ELF-EMF as a coadjutant in the treatment of several diseases related to oxidative damage as occurs in cancer [8,9]. The importance of the use of ELF-EMF-based therapies is precisely their low cost, safety, effectiveness, and their implication on the homeostasis of the biological systems (BS).…”