Study: Induction of apoptosis in B16‐BL6 melanoma cells following exposure to electromagnetic fields modeled after intercellular calcium waves.

The study “Induction of apoptosis in B16‐BL6 melanoma cells following exposure to electromagnetic fields modelled after intercellular calcium waves”

Title: Induction of Apoptosis in B16‐BL6 Melanoma Cells Following Exposure to Electromagnetic Fields Modelled After Intercellular Calcium Waves

Authors: Benjamin D. Rain, Adam D. Plourde-Kelly, Robert M. Lafrenie, & Blake T. Dotta

Institution: Behavioural Neuroscience & Biology Programs, School of Natural Science, Laurentian University, Sudbury, Ontario, Canada

Abstract: The study investigates the impact of time-varying electromagnetic fields (EMF) modelled after the physiological firing frequency of intercellular calcium waves on B16-BL6 melanoma cells. The researchers hypothesized that exposure to such EMFs could decrease the viability of these cells and promote apoptosis. The study used B16-BL6 cells due to their high prevalence of T-type voltage-gated calcium channels and compared them with HEK293 cells which have low levels of these channels.

 

Key Findings:

1. Reduction in Cell Viability: Exposure to a calcium (Ca2+) EMF for 40 minutes reduced the number of viable B16-BL6 cells by 50.3%. The study observed significant cellular apoptosis, pre-apoptotic cells, nuclear fragmentation, and increased spacing between cells in the Ca2+ EMF condition compared to the control.
2. Mechanism of Action: The study proposes that the EMFs work by enhancing reactive oxygen species presence, differentially activating cellular signaling cascades, and inducing rapid Ca2+ influx. These processes are thought to decrease cell growth and induce apoptosis.
3. Specificity of the EMF Effect: The effects were observed predominantly in B16-BL6 cells due to their high amount of T-type voltage-gated Ca2+ channels. HEK293 cells did not show significant effects, highlighting the specificity of the Ca2+ EMF mechanism.
4. Cell Imaging Results: Imaging with acridine orange and ethidium bromide dye showed substantial cellular apoptosis under the Ca2+ EMF condition. This suggests that the EMF treatment leads to both early and late apoptotic stages in the cells.
5. Interaction with Calcium Channel Activator: Cells treated with the BAY K8644 calcium channel activator and exposed to the Ca2+ EMF did not show a significant decrease in viable cells. This suggests that the EMF’s efficacy lies in altering the kinetic properties of L-type and T-type voltage-gated Ca2+ channels.

The study concludes that exposure to EMFs modeled after intercellular calcium waves can inhibit the proliferation of malignant cells and induce apoptosis. The findings support the hypothesis that complex-patterned EMFs can influence cellular behaviors and suggest that such EMF exposure could act as a potential anti-cancer therapy, specifically through alterations in T-type Ca2+ channel permeability.

Implications: This research adds to the growing body of evidence supporting the potential therapeutic applications of EMFs in cancer treatment. It highlights the possibility of using EMFs to target specific cellular mechanisms associated with cancer cell proliferation and survival, opening avenues for non-invasive and targeted cancer therapies.

 

Frequencies Used:

• • The study does not specify the exact frequencies in the text provided. However, it mentions that the EMF was modeled after the physiological firing pattern of calcium waves in murine cells. This implies that the frequencies were chosen to mimic the natural frequencies of calcium wave activity in these cells.

When the apoptosis study aimed to mimic these frequencies, they would have designed EMFs to cycle at similar rates – around 0.75 Hz for patterns resembling intracellular waves and approximately 1.37 Hz for patterns mimicking the bursting behavior of intercellular waves. These EMFs would have been time-varying to match the dynamic nature of calcium waves observed in the Hennig et al. study.

• • Calcium waves in biological systems can vary in frequency depending on the type of cells and the physiological processes involved. The study aimed to replicate the pattern, frequency, and temporal characteristics of these natural waves.

Intensity of EMF (1 microtesla):

• • The EMF used in the study had an intensity of 1 microtesla (uT). This is a measure of magnetic field strength. To put this in context, it’s important to compare it with common sources of magnetic fields, such as cell phones.
  • The magnetic fields produced by cell phones can vary widely depending on the model and usage. When talking on a cell phone, the magnetic field at the head level can range from 0.2 to 2 microteslas, with peaks potentially higher depending on the phone’s design and the network conditions. However, it’s crucial to note that these fields are not constant and diminish rapidly with distance from the device.

Comparison with Cell Phone Radiation:

• • Cell phone radiation is a form of non-ionizing electromagnetic radiation that includes both electric and magnetic fields (radiofrequency radiation). The magnetic field component of cell phone radiation is generally the same intensity compared to the 1 microtesla field used in the study.
  • The frequency of cell phone radiation is typically in the range of 700 MHz to 2.7 GHz, which is much higher than the low-frequency EMFs that would be associated with calcium wave activity in biological systems.  These frequencies are typically much lower than the primary carrier frequencies used in cell phone communication but may be similar to the modulation frequencies.

Digital Signal Modulation:

1. • Digital signals, like those used in cell phone communication, are often modulated onto a carrier wave. This carrier wave operates at a higher frequency, typically in the range of 700 MHz to 2.7 GHz for cell phones.
   • Modulation involves varying a property of the carrier wave (such as its amplitude, frequency, or phase) in accordance with the information (or signal) being transmitted. This is essential for effectively transmitting complex information over long distances.
2. Low-Frequency Modulation:
   • In some digital communication systems, including cell phones, the high-frequency carrier wave can be modulated with lower frequency signals. These lower frequencies can sometimes be in the Hz range, which is much closer to the natural frequencies of biological processes, such as calcium wave activity in cells.
   • This modulation is crucial because it allows the high-frequency carrier wave to convey complex information, such as voice or data, which can have components in the lower frequency range.
3. Relevance to the Study:
   • The study “Induction of apoptosis in B16‐BL6 melanoma cells following exposure to electromagnetic fields modelled after intercellular calcium waves” used EMFs specifically designed to mimic the natural frequencies of calcium wave activity in biological systems. These frequencies are typically much lower than the primary carrier frequencies used in cell phone communication but may be similar to the modulation frequencies.
   • The focus of the study was to explore whether EMFs, when patterned to mimic biological signals (like calcium waves), could have therapeutic effects, such as inducing apoptosis in cancer cells. This is distinct from the typical usage of EMFs in telecommunications.
4. Comparing to Cell Phone EMFs:
   • While cell phone EMFs operate primarily at higher carrier frequencies (MHz to GHz range), their modulation components can have lower frequencies. However, the biological effects of these modulated signals are a complex area of study and are influenced by various factors including the type of modulation, power level, duration of exposure, and the specific biological context.
   • The study on melanoma cells is an exploration into how specific low-frequency EMFs, designed to mimic biological processes, can affect cellular behavior.

 

To determine the specific frequencies used in the study “Induction of Apoptosis in B16‐BL6 Melanoma Cells Following Exposure to Electromagnetic Fields Modelled After Intercellular Calcium Waves,” we need to reference the frequencies of intracellular and intercellular Ca2+ waves from the study “Patterns of intracellular and intercellular Ca2+ waves in the longitudinal muscle layer of the murine large intestine In vitro” by Grant W Hennig et al.

Indeed, the frequencies identified in the study, around 0.75 Hz and 1.37 Hz, are comparable to the frequency range of a human heart rate under certain conditions. To put this into perspective:

• 0.75 Hz Frequency: This frequency translates to 45 cycles per minute (cpm), as there are 60 seconds in a minute. This is akin to a very relaxed or resting heart rate. For example, well-trained athletes might have resting heart rates around this frequency.

A frequency of 0.75 Hz corresponds to a wavelength of approximately 399,723,277 meters, or about 399.7 kilometers. Similar to the previous calculation, this is based on the speed of light in a vacuum and assumes that the wave in question is electromagnetic. In different mediums, or for waves of a different nature, the wavelength would vary even with the same frequency

• 1.37 Hz Frequency: This frequency equates to approximately 82 cycles per minute. This is within the range of a normal resting heart rate for adults, which typically lies between 60 to 100 beats per minute.

A frequency of 1.37 Hz corresponds to a wavelength of approximately 218,826,612 meters, or about 218.8 kilometers. This calculation is based on the formula for wave speed, where the wavelength ($\lambda$) is equal to the speed of light ($c$, approximately $299,792,458$ meters per second) divided by the frequency ($f$). This is under the assumption that the wave is electromagnetic and propagating in a vacuum. In other mediums, or for different types of waves, the propagation speed would be different, resulting in a different wavelength for the same frequency.

The parallel between these frequencies and the human heart rate is an interesting observation, especially considering the physiological role of both heart rate and calcium waves in the body:

• Heart Rate: The heart rate is a vital sign reflecting the number of times the heart beats per minute. It varies based on numerous factors, including physical activity, emotional state, and overall health.
• Calcium Waves: In contrast, calcium waves in cells, including those in the gastrointestinal tract, play a crucial role in various cellular processes. These waves can influence muscle contractions, signal transduction, and, as studied in the apoptosis research, potentially affect cancer cell viability.

The similarity in frequencies underscores a fundamental aspect of biological systems: many processes operate within similar frequency ranges, often dictated by the physical and chemical properties that govern cellular activities. In the case of the apoptosis study, replicating these natural, biologically relevant frequencies was key to exploring the therapeutic potential of EMFs in cancer treatment. This approach demonstrates a unique intersection of biology and physics, where understanding and mimicking natural biological rhythms can lead to potential medical advancements.

 

The human heart does generate a magnetic field, but it’s important to note that the field strength is quite weak compared to artificial electromagnetic fields. The heart’s magnetic field is primarily generated by the electrical activity that coordinates its contractions, specifically the depolarization and repolarization during the cardiac cycle.

The magnetic field strength of the human heart is typically measured in picoTesla (pT), which is a much smaller unit than microTesla (uT). For reference, 1 picoTesla is equal to 0.000001 microTesla.

The strength of the heart’s magnetic field is generally in the range of a few picoTeslas. More specifically, measurements taken with sensitive devices like Superconducting Quantum Interference Devices (SQUIDs), which are used in MagnetoCardioGraphy (MCG), typically detect cardiac magnetic fields in the order of 10 to 100 picoTesla.

In contrast, a microTesla is a unit more commonly used to measure stronger magnetic fields, such as those generated by electrical appliances, medical devices, or geomagnetic activity. For example, the Earth’s magnetic field strength is about 25 to 65 microTesla, which is several orders of magnitude stronger than the heart’s magnetic field.

So, while the heart does radiate a magnetic field, its strength is quite low and is measured in picoTesla, not microTesla.