Int. J. Environ. Res. Public Health 2010, 7, 938-965; doi:10.3390/ijerph7030938 OPEN ACCESS International Journal of Environmental Research and Public Health ISSN 1660-4601 www.mdpi.com/journal/ijerph Article Mechanisms of Geomagnetic Field Influence on Gene Expression Using Influenza as a Model System: Basics of Physical Epidemiology Valeriy Zaporozhan and Andriy Ponomarenko * Odessa State Medical University, Valekhovsky lane 2, 65082, Odessa, Ukraine; E-Mail: rector@odmu.edu.ua * Author to whom correspondence should be addressed; E-Mail: aponom@hotmail.com; Tel.: +380-96-900-9907; Fax: +380-48-723-2969. Received: 22 December 2009; in revised form: 14 January 2010/ Accepted: 22 February 2010 / Published: 10 March 2010 Abstract: Recent studies demonstrate distinct changes in gene expression in cells exposed to a weak magnetic field (MF). Mechanisms of this phenomenon are not understood yet. We propose that proteins of the Cryptochrome family (CRY) are "epigenetic sensors" of the MF fluctuations, i.e., magnetic field-sensitive part of the epigenetic controlling mechanism. It was shown that CRY represses activity of the major circadian transcriptional complex CLOCK/BMAL1. At the same time, function of CRY, is apparently highly responsive to weak MF because of radical pairs that periodically arise in the functionally active site of CRY and mediate the radical pair mechanism of magnetoreception. It is known that the circadian complex influences function of every organ and tissue, including modulation of both NF-κB- and glucocorticoids- dependent signaling pathways. Thus, MFs and solar cycles-dependent geomagnetic field fluctuations are capable of altering expression of genes related to function of NF-κB, hormones and other biological regulators. Notably, NF-κB, along with its significant role in immune response, also participates in differential regulation of influenza virus RNA synthesis. Presented data suggests that in the case of global application (example—geomagnetic field), MF-mediated regulation may have epidemiological and other consequences. Keywords: Solar cycles; electromagnetic fields; pair radical reactions; Cryptochrome; gene expression; NF-kB, influenza; epidemiology; circadian transcription