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Electromagnetic Fields in Biological Systems
7.5 Biological Effects at a Cellular
and Biomolecular Level
THz irradiation of human skin can cause thermal gradients that result in appreciable
increases in tissue temperature. These spatio-temporal thermal gradients are the driving
force for THz-induced skin damage (as discussed in Section 7.4.). In addition to damaging the tissue, these thermal gradients can also cause damage to resident skin cells (i.e.,
keratinocytes, fibroblasts, etc). In this section, we provide an overview of the cellular
processes that are typically activated in cells exposed to environmental stressors, such as
heat or THz radiation. We begin with a discussion of the core proteins and intracellular
signaling pathways that are associated with the cellular stress response (CSR). We then
discuss the biological effects that THz radiation causes at a cellular, organelle, and biomolecular level. Finally, we conclude with recent data, which suggests that human cells
express a signature gene expression profile when exposed to THz radiation.
7.5.1 Background on Cellular Stress Response
and Cellular Death
Mammalian cells frequently encounter conditions that can lead to stress. A few wellcharacterized external stressors include hyperthermia, hypothermia, hypoxia, ionizing
radiation, and EM energy. Internal stressors include ATP depletion, oxidative stress, and
pathogenic stimuli. At the molecular level, these stressors can exert strain on intracellular biomolecules (e.g., lipids, proteins, and DNA). If the applied strain is appreciable and
exceeds the cells homeostatic regulatory mechanisms, these biomolecules can undergo
structural modifications that preclude them from functioning properly. In addition, if
the magnitude of the strain exceeds the cell’s capacity for repair (i.e., irreversible damage), then such exposures can lead to cell death via apoptotic or necrotic mechanisms.
In order to survive and adapt to stressful conditions, all mammalian cells have
evolved a molecular defense reaction called the cellular stress response. The CSR is rapidly activated in response to stress and primarily involves the following intracellular
signaling pathways: redox, DNA sensing and repair, molecular chaperones, proteolysis, energy metabolism, and apoptosis (Kultz 2003). Many proteins are associated with
these pathways; however, a group of 44 evolutionary conserved proteins have recently
been identified as core mediators (Kultz 2005). These proteins, collectively referred to
as minimal stress proteins, are regulated by cells at both the transcriptional and posttranscriptional levels. At the transcription level, the mRNAs for these stress proteins
are transcribed for rapid de novo protein synthesis; whereas at the posttranscriptional
level, regulation is executed on the pool of existing mRNAs, where some are selected for
translation and others are suppressed.
When skin is exposed to THz radiation, resident skin cells may undergo reversible
and irreversible changes. A few common cellular and molecular effects include the following: activation of the CSR, cellular membrane deformation, cell death via necrotic
mechanisms, damage to ATP machinery, and DNA damage (Figure 7.20). When cells
are exposed to severe hyperthermic stress, they typically exhibit a signature stress
Electromagnetic Fields in Biological Systems
7.5 Biological Effects at a Cellular
and Biomolecular Level
THz irradiation of human skin can cause thermal gradients that result in appreciable
increases in tissue temperature. These spatio-temporal thermal gradients are the driving
force for THz-induced skin damage (as discussed in Section 7.4.). In addition to damaging the tissue, these thermal gradients can also cause damage to resident skin cells (i.e.,
keratinocytes, fibroblasts, etc). In this section, we provide an overview of the cellular
processes that are typically activated in cells exposed to environmental stressors, such as
heat or THz radiation. We begin with a discussion of the core proteins and intracellular
signaling pathways that are associated with the cellular stress response (CSR). We then
discuss the biological effects that THz radiation causes at a cellular, organelle, and biomolecular level. Finally, we conclude with recent data, which suggests that human cells
express a signature gene expression profile when exposed to THz radiation.
7.5.1 Background on Cellular Stress Response
and Cellular Death
Mammalian cells frequently encounter conditions that can lead to stress. A few wellcharacterized external stressors include hyperthermia, hypothermia, hypoxia, ionizing
radiation, and EM energy. Internal stressors include ATP depletion, oxidative stress, and
pathogenic stimuli. At the molecular level, these stressors can exert strain on intracellular biomolecules (e.g., lipids, proteins, and DNA). If the applied strain is appreciable and
exceeds the cells homeostatic regulatory mechanisms, these biomolecules can undergo
structural modifications that preclude them from functioning properly. In addition, if
the magnitude of the strain exceeds the cell’s capacity for repair (i.e., irreversible damage), then such exposures can lead to cell death via apoptotic or necrotic mechanisms.
In order to survive and adapt to stressful conditions, all mammalian cells have
evolved a molecular defense reaction called the cellular stress response. The CSR is rapidly activated in response to stress and primarily involves the following intracellular
signaling pathways: redox, DNA sensing and repair, molecular chaperones, proteolysis, energy metabolism, and apoptosis (Kultz 2003). Many proteins are associated with
these pathways; however, a group of 44 evolutionary conserved proteins have recently
been identified as core mediators (Kultz 2005). These proteins, collectively referred to
as minimal stress proteins, are regulated by cells at both the transcriptional and posttranscriptional levels. At the transcription level, the mRNAs for these stress proteins
are transcribed for rapid de novo protein synthesis; whereas at the posttranscriptional
level, regulation is executed on the pool of existing mRNAs, where some are selected for
translation and others are suppressed.
When skin is exposed to THz radiation, resident skin cells may undergo reversible
and irreversible changes. A few common cellular and molecular effects include the following: activation of the CSR, cellular membrane deformation, cell death via necrotic
mechanisms, damage to ATP machinery, and DNA damage (Figure 7.20). When cells
are exposed to severe hyperthermic stress, they typically exhibit a signature stress