Publication of the NTP study on DNA “damage” – hold your horses… do not jump to premature conclusions…

final update, added on October 24, 2019, is available at the end of this blog post…

Yesterday, October 21, 2019, the ‘Environmental and Molecular Mutagenesis‘ has published the peer-reviewed article of the effects of RF on DNA, obtained in the US NTP animal toxicology study.

As reported in the Microwave News, the NTP study authors concluded:

[S]ignificant increases in the levels of DNA damage measured by the comet assay were seen in several tissues from rats and mice, indicating that RFR may be capable of causing increases in DNA damage.”

While the results of the NTP study appear to be reliable, and BRHP-blog reported the first findings already in 2016 ( here ), we should not jump to any premature conclusions about the possible DNA-damaging (?) effects of RF exposure.

What the NTP study has found is the increase in the amount of damaged DNA in cells exposed to RF. However, it still is not known what caused the appearance of the damaged DNA. The NTP study did not look for the mechanism, causing increased amounts of damaged DNA in RF-exposed cells. This will be the topic of the future, already planned, research.

There are at least three possible options to explain the increase in the amount of damaged DNA:

  1. an unknown yet mechanism
  2. actual DNA damage caused by free radicals generated by RF exposure
  3. DNA “damage” occurred spontaneously and has nothing to do with the RF exposure, and the accumulation of the spontaneously “damaged” DNA was caused by RF-induced impairment of the cellular DNA repair pathways

About the plausibility of the first two potential mechanisms of DNA damage we do not know anything yet. However, the third option of the “damage” unrelated to RF exposure finds some support in the study on the DNA damage caused by the ELF-EMF exposures. As Focke et al. (Mutation Research, 2010) have shown, the increased amounts of “damaged” DNA in ELF-EMF exposed cells were caused not by the ELF-EMF but were result of ELF-EMF-induced inhibition of the repair of the spontaneously damaged DNA.

Summa summarum, it is known that the exposures to RF-EMF and to ELF-EMF correlate with the increase of the amount of damaged DNA in cells. In case of ELF-EMF it was shown that ELF-EMF exposure itself (directly or indirectly) does not cause DNA damage but it inhibits DNA repair mechanisms. Whether it is, or not, similarly the case with RF-EMF, requires further study.

In conclusion, what is known about the RF-EMF impact on DNA (see slide below) is not enough to claim mutagenicity or genetoxicity, yet. Of the paramount importance is to find out what happens to the “damaged” DNA – is it repaired or is it inherited by the next generations of cells.

Final update:

Genotoxicity describes the property of, chemical or physical, agents that damages the genetic information within a cell. This genotoxic damage may cause mutations, which may lead to cancer. However, while all mutagens are genotoxic, not all genotoxic substances are mutagenic.

In respect to the NTP study:

  1. The authors do not know if RF is really genotoxic. Observed DNA damage might have been “damaged” spontaneously, what happens in cells all the time, and not by RF. Thus, their claim of genotoxicity of RF is premature and is lacking scientific evidence.
  2. The authors do not know what happens to the “damaged” DNA, is it repaired or does it turn into mutation, hence, the authors have no idea whether RF is, or not, mutagenic. Also, not every mutation equals cancer.
  3. What the authors have shown is the increase in the amounts of “damaged” DNA that while correlate with the RF exposure are by itself not a proof of causality. As long as there is no answer as what caused the DNA “damage” and what is the fate of the “damaged” DNA, judging the physiological significance of this observation is not possible.

RESEARCH NEEDS TO CONTINUE…

12 thoughts on “Publication of the NTP study on DNA “damage” – hold your horses… do not jump to premature conclusions…

  1. Hi, Dariusz,

    Why did the study choose for example 6W / kg, since such a power does not apply to the phone used by people?

  2. Thanks for answering. I could miss some qualified comment on the quantity of dna breaks reported in the study.

  3. Nope. DNA damage quality and quantity matters. What matters a lot is also what happens to damaged DNA. Is it repaired or is it inherited by cell descendants. It all matters a lot.

  4. As i find the “impaired DNA repair” hypotheses intriguing it doesn’t really matter. The NTP was a controlled study with a significant causal effect. DNA damage happened. That’s just a bad thing I’m sure you’ll agree. We do not need more research in regards to human health. Thank you for doing such a great job getting the message out 🙂

  5. Thank you for your nice analysis Mr Leszczynski.
    while the rat data seems to be at least in part consistent with the outcome of the NTP study for male rats, the mouse data does not fit well to the overall conclusion of the NTP regarding mice.
    Do you have any comment on the extremely low mean value and interanimal variability of the shared control group in the male mouse frontal cortex data (0.63 ± 0.08 mean tail DNA). Please have a look on SUPPORTING INFORMATION figures 4C and 4D of the paper. I am not an expert for comet assay data, but when compared to data of female mice and data of the other tissues, the (male mice frontal cortex shared control) data seems to be far from what can be expected normally. Apart from this data there are no other (control) data with such low mean value and standard deviation.
    For me, a sample of 5 mice per group seems to be a little bit too small to exclude the possibility that the pubished control data in the paper just sampled the low damage part of the whole ensemble. As a GSM & CDMA shared control group was used, the outcome of both modulations could be dominated by such an effect.

  6. You are absolutely correct. Clarifying sentence was added, for those not aware of this fact

  7. Thanks Dariusz. Although you point this out, it is important to emphasize that the mutations, although correlated with RFR exposure, can just be mutations and never lead to cancer (there are many things that cause an increase in mutations that nobody ever worries about). There still remains limited evidence of the latter.

  8. In genetics, genotoxicity describes the property of chemical agents that damages the genetic information within a cell causing mutations, which may lead to cancer. While genotoxicity is often confused with mutagenicity, all mutagens are genotoxic, whereas not all genotoxic substances are mutagenic.
    1. The authors do not know if RF is really genotoxic (DNA might be damaged spontaneously and not by RF). Their claim of genotoxicity is lacking scientific evidence.
    2. They do not know what happens to damaged DNA, hence, have no idea whether RF is mutagenic.

  9. The dead ones doesn’t really care if it was homicide or heart attack. Broken DNA’s would probably agree if they could speak. After all – dead is dead, broken is broken?

    Quoting page 20:
    “However, our results and the results of other experiments suggest that non-thermal exposure of cells or whole organisms to RFR may result in measurable genotoxic effects, despite varied and weak responses across studies overall.”

    It’s likely that the authors takes the correlation as a genotoxic finding. You: Only correlation.

    But what is the important difference?

  10. I have seen discussion about RFR directly exciting resonance within the DNA molecule, causing molecular damage.
    I also have a pet theory that structured water may play a role here, whereby RFR excites resonant frequencies within the intracellular water matrix, disrupting the ‘grid’ of water molecules within the cell and impacting the organels.
    https://resonance.is/chiral-water-super-structure-forms-around-dna/

    If you just put a lump of meat in the microwave oven for a minute or two, you’ll see a plate full of water. This water wasn’t present as liquid water before the experiment, so it must have been present in a different ‘state’ within the tissue.

    Thoughts?

  11. There are several papers indicating that RFR-induced DNA damage is caused by free radicals (see list below). They are based mainly on the observations: 1. an increase in oxidative-DNA damage after RFR exposure; and 2. effects could be blocked by antioxidants. Similar results have also been found after exposure to static- and ELF-EMF (see supplementary material in Lai, H. Electromagnetic Biology and Medicine 38:231-248, 2019.) Yes, it is still a question on whether DNA damage could transform into mutation leading to cancer and other diseases.

    The three mechanisms Dariusz mentioned are not mutually exclusive ana d should be investigated individually.

    Henry Lai

    RFR-induced DNA damage and free radicals
    Agarwal A, Desai NR, Makker K, Varghese A, Mouradi R, Sabanegh E, Sharma R. Effects of radiofrequency electromagnetic waves (RF-EMW) from cellular phones on human ejaculated semen: an in vitro pilot study. Fertil Steril. 92(4) 1318-1325, 2009.
    Alkis ME, Bilgin HM, Akpolat V, Dasdag S, Yegin K, Yavas MC, Akdag MZ. Effect of 900-, 1800-, and 2100-MHz radiofrequency radiation on DNA and oxidative stress in brain. Electromagn Biol Med. 38(1):32-47, 2019.
    Atasoy HI, Gunal MY, Atasoy P, Elgun S, Bugdayci G. Immunohistopathologic demonstration of deleterious effects on growing rat testes of radiofrequency waves emitted from conventional Wi-Fi devices. J Pediatr Urol. 9(2): 223-229, 2013.
    Bourdineaud JP, Šrut M, Štambuk A, Tkalec M, Brèthes D, Malarić K, Klobučar GIV. Electromagnetic fields at a mobile phone frequency (900 MHz) trigger the onset of general stress response along with DNA modifications in Eisenia fetida earthworms. Arh Hig Rada Toksikol. 68(2):142-152, 2017.
    Burlaka A, Tsybulin O, Sidorik E, Lukin S, Polishuk V, Tsehmistrenko S, Yakymenko I. Overproduction of free radical species in embryonal cells exposed to low intensity radiofrequency radiation. Exp Oncol. 35(3):219-225, 2013.
    Campisi A, Gulino M, Acquaviva R, Bellia P, Raciti G, Grasso R, Musumeci F, Vanella A, Triglia A. Reactive oxygen species levels and DNA fragmentation on astrocytes in primary culture after acute exposure to low intensity microwave electromagnetic field. Neurosci Lett. 473(1):52-55, 2010.
    De Iuliis GN, Newey RJ, King BV, Aitken RJ. Mobile Phone Radiation Induces Reactive Oxygen Species Production and DNA Damage in Human Spermatozoa In Vitro. PLoS ONE 4(7): e6446, 2009. doi:10.1371/journal.pone.0006446
    Duan W, Liu C, Zhang L, He M, Xu S, Chen C, Pi H, Gao P, Zhang Y, Zhong M, Yu Z, Zhou Z. Comparison of the Genotoxic Effects Induced by 50 Hz Extremely Low-Frequency Electromagnetic Fields and 1800 MHz Radiofrequency Electromagnetic Fields in GC-2 Cells. Radiat Res. 183(3):305-314, 2015.
    Gajski G, Garaj-Vrhovac V. Radioprotective effects of honeybee venom (Apis mellifera) against 915-MHz microwave radiation-induced DNA damage in wistar rat lymphocytes: in vitro study. Int J Toxicol. 28(2):88-98, 2009.
    Guler G, Tomruk A, Ozgur E, Seyhan N. The effect of radiofrequency radiation on DNA and lipid damage in non-pregnant and pregnant rabbits and their newborns. Gen Physiol Biophys. 29(1):59-66, 2010.
    Güler G, Tomruk A, Ozgur E, Sahin D, Sepici A, Altan N, Seyhan N. The effect of radiofrequency radiation on DNA and lipid damage in female and male infant rabbits. Int J Radiat Biol. 88(4):367-373, 2012.
    Gürler HS, Bilgici B, Akar AK, Tomak L, Bedir A. Increased DNA oxidation (8-OHdG) and protein oxidation (AOPP) by Low level electromagnetic field (2.45 GHz) in rat brain and protective effect of garlic. Int J Radiat Biol. 2014 May 21:1-15. [Epub ahead of print]
    Hancı H, Odacı E, Kaya H, Aliyazıcıoğlu Y, Turan I, Demir S, Colakoğlu S. The effect of prenatal exposure to 900-MHz electromagnetic field on the 21-old-day rat testicle. Reprod Toxicol. 42:203-209, 2013.
    Hatice Ş. Gürler, Birşen Bilgici, Ayşegül K. Akar, Leman Tomak & Abdülkerim Bedir. Increased DNA oxidation (8-OHdG) and protein oxidation (AOPP) by low level electromagnetic field (2.45 GHz) in rat brain and protective effect of garlic. International Journal of Radiation Biology. Posted online on August 4, 2014.
    Khalil AM, Gagaa MH, Alshamali AM. 8-Oxo-7, 8-dihydro-2′-deoxyguanosine as a biomarker of DNA damage by mobile phone radiation. Hum Exp Toxicol. 31(7):734-740, 2012.
    Kumar S, Nirala JP, Behari J, Paulraj R. Effect of electromagnetic irradiation produced by 3G mobile phone on male rat reproductive system in a simulated scenario. Indian J Exp Biol. 52(9):890-897, 2014.
    Lai, H, Singh, NP, Melatonin and a spin-trap compound block radiofrequency electromagnetic radiation-induced DNA strand breaks in rat brain cells. Bioelectromagnetics 18(6):446-454, 1997.
    Liu C, Duan W, Xu S, Chen C, He M, Zhang L, Yu Z, Zhou Z. Exposure to 1800 MHz radiofrequency electromagnetic radiation induces oxidative DNA base damage in a mouse spermatocyte-derived cell line. Toxicol Lett 218(1): 2-9, 2013.
    Luukkonen J, Hakulinen P, Mäki-Paakkanen J, Juutilainen J, Naarala J. Enhancement of chemically induced reactive oxygen species production and DNA damage in human SH-SY5Y neuroblastoma cells by 872MHz radiofrequency radiation. Mutat Res. 662(1-2):54-58, 2009.
    Meena R, Kumari K, Kumar J, Rajamani P, Verma HN, Kesari KK. Therapeutic approaches of melatonin in microwave radiations-induced oxidative stress-mediated toxicity on male fertility pattern of Wistar rats Electromagn Biol Med. 33(2):81-91, 2014.
    Pandey N, Giri S. Melatonin attenuates radiofrequency radiation (900 MHz)-induced oxidative stress, DNA damage and cell cycle arrest in germ cells of male Swiss albino mice. Toxicol Ind Health. 34(5):315-327, 2018.
    Şahin D, Özgür E, Güler G, Tomruk A, Ünlü İ, Sepici-Dinçel A, Seyhan N. The 2100MHz radiofrequency radiation of a 3G-mobile phone and the DNA oxidative damage in brain. J Chem Neuroanat. 2016 Jan 8. pii: S0891-0618(16)00004-1. doi: 10.1016/j.jchemneu.2016.01.002. [Epub ahead of print]
    Shahin S, Singh VP, Shukla RK, Dhawan A, Gangwar RK, Singh SP, Chaturvedi CM. 2.45 GHz microwave irradiation-induced oxidative stress affects implantation or pregnancy in mice, Mus musculus. Appl Biochem Biotechnol. 169(5):1727-1751, 2013.
    Sokolovic D, Djordjevic B, Kocic G, Stoimenov TJ, Stanojkovic Z, Sokolovic DM, et al. The Effects of Melatonin on Oxidative Stress Parameters and DNA Fragmentation in Testicular Tissue of Rats Exposed to Microwave Radiation. Adv Clin Exp Med. 24(3):429-436, 2015.
    Sun Y, Zong L, Gao Z, Zhu S, Tong J, Cao Y. Mitochondrial DNA damage and oxidative damage in HL-60 cells exposed to 900MHz radiofrequency fields. Mutat Res. 797-799:7-14, 2017.
    Tkalec M, Stambuk A, Srut M, Malarić K, Klobučar GI. Oxidative and genotoxic effects of 900 MHz electromagnetic fields in the earthworm Eisenia fetida. Ecotoxicol Environ Saf. 90:7-12, 2013.
    Tomruk A, Guler G, Dincel AS. The influence of 1800 MHz GSM-like signals on hepatic oxidative DNA and lipid damage in nonpregnant, pregnant, and newly born rabbits. Cell Biochem Biophys. 56(1):39-47, 2010.
    Wang X, Liu C, Ma Q, Feng W, Yang L, Lu Y, Zhou Z, Yu Z, Li W, Zhang L. 8-oxoG DNA Glycosylase-1 Inhibition Sensitizes Neuro-2a Cells to Oxidative DNA Base Damage Induced by 900 MHz Radiofrequency Electromagnetic Radiation. Cell Physiol Biochem. 37(3):1075-1088, 2015.
    Xu S, Zhou Z, Zhang L, Yu Z, Zhang W, Wang Y, Wang X, Li M, Chen Y, Chen C, He M, Zhang G, Zhong M. Exposure to 1800 MHz radiofrequency radiation induces oxidative damage to mitochondrial DNA in primary cultured neurons. Brain Res. 1311:189-196, 2010.

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