The role of heme in environmentally caused oncogenesis (review)

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Abstract

The association of hemoblastoses, tumours of the central nervous system, with several other human neoplasms with various environmental factors of a chemical and physical nature has been previously established. Nonetheless, the mechanism of this relationship remains unclear. The author formulated the concept of environmentally determined oncogenesis with a key role of heme. According to the proposed model, the first stage of oncogenesis is the induction of environmentally determined oxidative stress, which is amplified by haem iron. Simultaneously, due to the ferromagnetic properties of heme iron reception, the induction and amplification of external electromagnetic fields occur with the formation of a feedback loop and additional stimulation of oxidative processes. Further, under the influence of active oxygen metabolites in target tissues with the greatest contact with heme, epigenomic dysregulation of semaphorin is developed. This leads to oncogenesis in actively proliferating cells of the axon growth cone, bone marrow, precursors of kidney cells, mesenchymal stem cells and endothelium. Consequently, benign tumours of the endothelium (hemangiomas), leukemias, lymphomas, tumours of the peripheral and central nervous system, as well as benign and malignant tumours of soft tissues occur. The proposed model illustrates the features of childhood oncology incidence with a predominance of hemangiomas among benign tumours, as well as hemoblastoses and tumours of the nervous system among cancers. In addition, the ability of heme to interact with electromagnetic fields advances our understanding of the relationship between neoplasms and solar activity.

About the authors

Sergey K. Pinaev

Far Eastern State Medical University; Khabarovsk Federal Research Center

Author for correspondence.
Email: pinaev@mail.ru
ORCID iD: 0000-0003-0774-2376
SPIN-code: 3986-4244
Scopus Author ID: 56291097200
ResearcherId: J-5942-2018

MD, Cand. Sci. (Med.), associate professor

Russian Federation, Khabarovsk; Khabarovsk

References

  1. Agadzhanyan NA, Chischov AYa, Kim TA. Diseases of civilization. Ekologiya cheloveka (Human Ecology). 2003;(4):8–11. (In Russ).
  2. Pinaev SK, Chizhov AYa, Pinaeva OG. Critical periods of adaptation to smoke and solar activity at the stages of ontogeny (review). Ekologiya cheloveka (Human Ecology). 2021;28(11):4–11. (In Russ). doi: 10.33396/1728-0869-2021-11-4-11
  3. Nelson L, Valle J, King G, et al. Estimating the proportion of childhood cancer cases and costs attributable to the environment in California. Am J Public Health. 2017;107(5):756–762. doi: 10.2105/AJPH.2017.303690
  4. World Health Organization. IARC Monographs on the Identification of Carcinogenic Hazards to Humans. List of Classifications. Agents classified by the IARC Monographs, Volumes 1–131. [cited 2022 Dec 06]. Available from: https://monographs.iarc.fr/list-of-classifications
  5. Pinaev SK, Chizhov AYa, Pinaeva OG. The link of smoke and solar activity with human neoplasms. Kazan Medical Journal. 2022;103(4):650–657. (In Russ). doi: 10.17816/KMJ2022-650
  6. Pinaev SK, Chizhov AYa, Pinaeva OG. The links between solar activity and smoke with trends in hematological malignancies in Russia. Radiation and Risk. 2022;31(3):100–110. (In Russ). doi: 10.21870/0131-3878-2022-31-3-100-110
  7. ONCOLOGY.RU [Internet]. Malignant neoplasms in Russia [cited 2023 Jan 17]. Available from: http://www.oncology.ru/service/statistics/malignant_tumors/ (In Russ).
  8. Chizhov AYa, Pinaev SK, Savin SZ. Environmentally-related oxidative stress as a carcinogenesis factor. Technologies of Living Systems. 2012;9(1):47–53. (In Russ).
  9. Abbasova MT, Gadzhiev AM. The influence of low-intensity electromagnetic radiation of the decimeter range on the indicators of iron in serum in rats. In: VIII International Congress "Weak and superweak fields and radiation in biology and medicine". Proceedings of the Congress; 2018 Sep 10–14; Saint Petersburg. Saint Petersburg: Sintez; 2018. P. 100. (In Russ).
  10. Korolnek T, Hamza I. Like iron in the blood of the people: the requirement for heme trafficking in iron metabolism. Front Pharmacol. 2014;5:126. doi: 10.3389/fphar.2014.00126
  11. Paul BT, Manz DH, Torti FM, Torti SV. Mitochondria and Iron: current questions. Expert Rev Hematol. 2017;10(1):65–79. doi: 10.1080/17474086.2016.1268047
  12. Sozarukova MM. Erythrocytes as sources and targets of free radicals. In: Vladimirova YuA, editor. Sources and targets of free radicals in human blood. Moscow: MAKS Press; 2017. P. 140–178. (In Russ).
  13. Lukina EA, Dezhenkova AV. Iron metabolism in normal and pathological conditions. Clinical oncohematology. 2015;8(4):355–361. (In Russ). doi: 10.21320/2500-2139-2015-8-4-355-361
  14. Ivanov SD. Iron and cancer: the role of iron ions in carcinogenesis and radiation therapy of tumor bearings. Uspekhi sovremennoy biologii. 2013;133(5):481–494. (In Russ).
  15. Keppner A, Maric D, Correia M, et al. Lessons from the post-genomic era: globin diversity beyond oxygen binding and transport. Redox Biol. 2020;37:101687. doi: 10.1016/j.redox.2020.101687
  16. Thévenod F. Iron and its role in cancer defense: a double-edged sword. Met Ions Life Sci. 2018;18. doi: 10.1515/9783110470734-021
  17. Kriventsev YuA, Bisalieva RA, Noskov AI. Human hemoglobins. Vestnik of Astrakhan State Technical University. 2007;(6):34–41. (In Russ).
  18. Sergunova VA, Manchenko EA, Gudkova OE. Hemoglobin: modification, crystallization, polymerization (review). General Reanimatology. 2016;12(6):49–63. doi: 10.15360/1813-9779-2016-6-49-63. (In Russ).
  19. Pfeifhofer-Obermair C, Tymoszuk P, Petzer V, et al. Iron in the tumor microenvironment-connecting the dots. Front Oncol. 2018;8:549. doi: 10.3389/fonc.2018.00549
  20. Galaris D, Barbouti A, Pantopoulos K. Iron homeostasis and oxidative stress: an intimate relationship. Biochim Biophys Acta Mol Cell Res. 2019;1866(12):118535. doi: 10.1016/j.bbamcr.2019.118535
  21. Muravlyova LE, Molotov-Luchanskiy VB, Klyuev DA, et al. Proteins of red blood cells. Minireview. Advances in Current Natural Sciences. 2013;(4):28–31. (In Russ).
  22. Fossen Johnson S. Methemoglobinemia: infants at risk. Curr Probl Pediatr Adolesc Health Care. 2019;49(3):57–67. doi: 10.1016/j.cppeds.2019.03.002
  23. Nesterov JuV, Teplyj DD. Morfofiziologicheskie pokazateli jeritrocitov pri oksidativnom stresse na raznyh jetapah ontogeneza. Zhivye i biokosnye sistemy. 2015;11. (In Russ). Available from: https://elibrary.ru/item.asp?id=24883113
  24. Agadzhanyan NA, Makarova II. Earth's magnetic field and the human body. Ekologiya cheloveka (Human Ecology). 2005;(9):3–9. (In Russ).
  25. Bondar GV, Shevchenko VV, Poljakov PI, Ryumshina TA. Influence of the magnetic field on blood counts. In: IX International Crimean Conference “Cosmos and biosphere”; Koktebel', 2011. Available from: http://www.biophys.ru/archive/crimea2011/abstr-p168.pdf (In Russ).
  26. Aleksandrov BL, Aleksandrov AZh. The mechanism of human exposure to the magnetic field of the Earth and the Sun. Polythematic online scientific journal of Kuban State Agrarian University. 2017;127:138–149. (In Russ). doi: 10.21515/1990-4665-127-006
  27. Grishin AN, Kornelik SE, Ryazantseva NV, Sychev OF. Biophysics of blood flow in strong magnetic fields: innovations and latest research. In: Innovations — 2009: collection of materials of the V All-Russian Scientific and Practical Conference of Students, Postgraduates and Young Scientists; 2009 May 14–15; Tomsk, 2009. P. 20–25. (In Russ).
  28. Obridko VN, Ragulskaya MV, Khabarova OV, et al. Cosmophysical factors of evolution of biosphere: new lines of research. Psychosomatic and Integrative Research. 2015;1(1):101. (In Russ).
  29. Khabarova OV, Dimitrova S. On the nature of people’s reaction to space weather and meteorological weather changes. Sun and Geosphere. 2009;4(2):60–71.
  30. Ragul'skaja MV, Habarova OV, Obridko VN, Dmitrieva IV. Vlijanie solnechnyh vozmushhenij na funkcionirovanie i sinhronizaciju chelovecheskogo organizma. Journal of Radio Electronics. 2000;(10):5. (In Russ). Available from: https://www.elibrary.ru/item.asp?id=15111655
  31. Chizhevskij AL. Strukturnyj analiz dvizhushhejsja krovi. Izdatel'stvo Akademii nauk SSSR; 1959. 474 p. (In Russ).
  32. Kopyltsov AV. Two-dimensional model of the distribution of the magnetic field between erythrocytes in a narrow capillary. Engineering Journal of Don. 2017;(4):88. (In Russ). Available from: https://www.elibrary.ru/item.asp?id=32731169
  33. García-Guede Á, Vera O, Ibáñez-de-Caceres I. When oxidative stress meets epigenetics: implications in cancer development. Antioxidants (Basel). 2020;9(6):468. doi: 10.3390/antiox9060468
  34. Volkov NM. Epigenetics: perspectives of targeted therapy. Practical Oncology. 2022;23(3):170–174. (In Russ). doi: 10.31917/2303170
  35. Chen H, Xie GH, Wang WW, et al. Epigenetically downregulated Semaphorin 3E contributes to gastric cancer. Oncotarget. 2015;6(24):20449–20465. doi: 10.18632/oncotarget.3936
  36. Xue W, Wang F, Han P, et al. The oncogenic role of LncRNA FAM83C-AS1 in colorectal cancer development by epigenetically inhibits SEMA3F via stabilizing EZH2. Aging (Albany NY). 2020;12(20):20396–20412. doi: 10.18632/aging.103835
  37. Tomizawa Y, Sekido Y, Kondo M, et al. Inhibition of lung cancer cell growth and induction of apoptosis after reexpression of 3p21.3 candidate tumor suppressor gene SEMA3B. Proc Natl Acad Sci U S A. 2001;98(24):13954–13959. doi: 10.1073/pnas.231490898
  38. Kundu A, Nam H, Shelar S, et al. PRDM16 suppresses HIF-targeted gene expression in kidney cancer. J Exp Med. 2020;217(6):e20191005. doi: 10.1084/jem.20191005
  39. Tischoff I, Markwarth A, Witzigmann H, et al. Allele loss and epigenetic inactivation of 3p21.3 in malignant liver tumors. Int J Cancer. 2005;115(5):684–689. doi: 10.1002/ijc.20944
  40. Abuetabh Y, Tiwari S, Chiu B, Sergi C. Semaphorins biology and their significance in cancer. Austin J Clin Pathol. 2014;1(2):1009.
  41. Fayyad-Kazan M, Najar M, Fayyad-Kazan H, et al. Identification and evaluation of new immunoregulatory genes in mesenchymal stromal cells of different origins: comparison of normal and inflammatory conditions. Med Sci Monit Basic Res. 2017;23:87–96. doi: 10.12659/msmbr.903518
  42. Neufeld G, Mumblat Y, Smolkin T, et al. The semaphorins and their receptors as modulators of tumor progression. Drug Resist Updat. 2016;29:1–12. doi: 10.1016/j.drup.2016.08.001
  43. Nasarre P, Gemmill RM, Drabkin HA. The emerging role of class-3 semaphorins and their neuropilin receptors in oncology. Onco Targets Ther. 2014;7:1663–1687. doi: 10.2147/OTT.S37744
  44. Neufeld G, Mumblat Y, Smolkin T, et al. The role of the semaphorins in cancer. Cell Adh Migr. 2016;10(6):652–674. doi: 10.1080/19336918.2016.1197478
  45. Jiang H, Tang J, Qiu L, et al. Semaphorin 4D is a potential biomarker in pediatric leukemia and promotes leukemogenesis by activating PI3K/AKT and ERK signaling pathways. Oncol Rep. 2021;45(4):1. doi: 10.3892/or.2021.7952
  46. Delloye-Bourgeois C, Bertin L, Thoinet K, et al. Microenvironment-driven shift of cohesion/detachment balance within tumors induces a switch toward metastasis in neuroblastoma. Cancer Cell. 2017;32(4):427–443.e8. doi: 10.1016/j.ccell.2017.09.006
  47. Torti SV, Torti FM. Iron and cancer: 2020 vision. Cancer Res. 2020;80(24):5435–5448. doi: 10.1158/0008-5472.CAN-20-2017
  48. Wang F, Lv H, Zhao B, et al. Iron and leukemia: new insights for future treatments. J Exp Clin Cancer Res. 2019;38(1):406. doi: 10.1186/s13046-019-1397-3
  49. Fonseca-Nunes A, Jakszyn P, Agudo A. Iron and cancer risk — a systematic review and meta-analysis of the epidemiological evidence. Cancer Epidemiol Biomarkers Prev. 2014;23(1):12–31. doi: 10.1158/1055-9965.EPI-13-0733

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2. Fig. 1. Scheme of environmentally-related oncogenesis: PM2.5 and PM10 — carbon particles 10 µm and 2.5 µm in size, respectivelz; PAHs — polycyclic aromatic hydrocarbons; ROS — reactive oxygen species; EMF — electromagnetic fields; ST — soft tissues.

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