Radiosensitivity

Radiosensitivity is the relative susceptibility of cells, tissues, organs or organisms to the harmful effect of ionizing radiation.

Cells types affected

Cells are least sensitive when in the S phase, then the G1 phase, then the G2 phase, and most sensitive in the M phase of the cell cycle. This is described by the 'law of Bergonié and Tribondeau', formulated in 1906: X-rays are more effective on cells which have a greater reproductive activity.[1][2]

From their observations, they concluded that quickly dividing tumor cells are generally more sensitive than the majority of body cells. This is not always true. Tumor cells can be hypoxic and therefore less sensitive to X-rays because most of their effects are mediated by the free radicals produced by ionizing oxygen.

It has meanwhile been shown that the most sensitive cells are those that are undifferentiated, well nourished, dividing quickly and highly active metabolically. Amongst the body cells, the most sensitive are spermatogonia and erythroblasts, epidermal stem cells, gastrointestinal stem cells.[3] The least sensitive are nerve cells and muscle fibers.

Very sensitive cells are also oocytes and lymphocytes, although they are resting cells and do not meet the criteria described above. The reasons for their sensitivity are not clear.

There also appears to be a genetic basis for the varied vulnerability of cells to ionizing radiation.[4] This has been demonstrated across several cancer types and in normal tissues.[5][6]

Cell damage classification

The damage to the cell can be lethal (the cell dies) or sublethal (the cell can repair itself). Cell damage can ultimately lead to health effects which can be classified as either Tissue Reactions or Stochastic Effects according to the International Commission on Radiological Protection.

Tissue reactions

Tissue reactions have a threshold of irradiation under which they do not appear and above which they typically appear. Fractionation of dose, dose rate, the application of antioxidants and other factors may affect the precise threshold at which a tissue reaction occurs. Tissue reactions include skin reactions (epilation, erythema, moist desquamation), cataracts, circulatory disease, and other conditions. Seven proteins were discovered in a systematic review, which correlated with radiosensitivity in normal tissues: γH2AX, TP53BP1, VEGFA, CASP3, CDKN2A, IL6, and IL1B. [7][8]

Stochastic effects

Stochastic effects do not have a threshold of irradiation, are coincidental, and cannot be avoided. They can be divided into somatic and genetic effects. Among the somatic effects, secondary cancer is the most important. It develops because radiation causes DNA mutations directly and indirectly. Direct effects are those caused by ionizing particles and rays themselves, while the indirect effects are those that are caused by free radicals, generated especially in water radiolysis and oxygen radiolysis. The genetic effects confer the predisposition of radiosensitivity to the offspring.[9] The process is not well understood yet.

Target structures

For decades, the main cellular target for radiation induced damage was thought to be the DNA molecule.[10] This view has been challenged by data indicating that in order to increase survival, the cells must protect their proteins, which in turn repair the damage in the DNA.[11] An important part of protection of proteins (but not DNA) against the detrimental effects of reactive oxygen species (ROS), which are the main mechanism of radiation toxicity, is played by non-enzymatic complexes of manganese ions and small organic metabolites.[11] These complexes were shown to protect the proteins from oxidation in vitro[12] and also increased radiation survival in mice.[13] An application of the synthetically reconstituted protective mixture with manganese was shown to preserve the immunogenicity of viral and bacterial epitopes at radiation doses far above those necessary to kill the microorganisms, thus opening a possibility for a quick whole-organism vaccine production.[14] The intracellular manganese content and the nature of complexes it forms (both measurable by electron paramagnetic resonance) were shown to correlate with radiosensitivity in bacteria, archaea, fungi and human cells.[15] An association was also found between total cellular manganese contents and their variation, and clinically-inferred radioresponsiveness in different tumor cells, a finding that may be useful for more precise radiodosages and improved treatment of cancer patients.[16]

See also

References

  1. ↑ Bergonié J, Tribondeau L (1906). "De Quelques Résultats de la Radiotherapie et Essai de Fixation d'une Technique Rationnelle". Comptes Rendus des Séances de l'Académie des Sciences. 143: 983–985.
  2. ↑ Bergonié, J.; Tribondeau, L. (1959). "Interpretation of Some Results of Radiotherapy and an Attempt at Determining a Logical Technique of Treatment / De Quelques Résultats de la Radiotherapie et Essai de Fixation d'une Technique Rationnelle". Radiation Research. 11 (4): 587–588. doi:10.2307/3570812. JSTOR 3570812.
  3. ↑ Trowell OA (October 1952). "The sensitivity of lymphocytes to ionising radiation". The Journal of Pathology and Bacteriology. 64 (4): 687–704. doi:10.1002/path.1700640403. PMID 13000583.
  4. ↑ Fornalski KW (2019). "Radiation adaptive response and cancer: from the statistical physics point of view". Physical Review E. 99 (2): 022139. Bibcode:2019PhRvE..99b2139F. doi:10.1103/PhysRevE.99.022139. PMID 30934317. S2CID 91187501.
  5. ↑ Yard BD, Adams DJ, Chie EK, Tamayo P, Battaglia JS, Gopal P, et al. (April 2016). "A genetic basis for the variation in the vulnerability of cancer to DNA damage". Nature Communications. 7: 11428. Bibcode:2016NatCo...711428Y. doi:10.1038/ncomms11428. PMC 4848553. PMID 27109210.
  6. ↑ Barnett GC, Coles CE, Elliott RM, Baynes C, Luccarini C, Conroy D, et al. (January 2012). "Independent validation of genes and polymorphisms reported to be associated with radiation toxicity: a prospective analysis study". The Lancet. Oncology. 13 (1): 65–77. doi:10.1016/S1470-2045(11)70302-3. PMID 22169268.
  7. ↑ Subedi, Prabal; Gomolka, Maria; Moertl, Simone; Dietz, Anne (2021). "Ionizing Radiation Protein Biomarkers in Normal Tissue and Their Correlation to Radiosensitivity: A Systematic Review". Journal of Personalized Medicine. 11 (2): 140. doi:10.3390/jpm11020140. PMC 7922485. PMID 33669522.
  8. ↑ Dietz, Anne; Gomolka, Maria; Moertl, Simone; Subedi, Prabal (2020). "Ionizing Radiation Protein Biomarkers in Normal Tissue and Their Correlation to Radiosensitivity: Protocol for a Systematic Review". Journal of Personalized Medicine. 11 (1): 3. doi:10.3390/jpm11010003. PMC 7822013. PMID 33375047.
  9. ↑ Fornalski KW (2016). "Radiation and evolution: from Lotka-Volterra equation to balance equation". International Journal of Low Radiation. 10 (3): 222–33. doi:10.1504/IJLR.2016.10002388.
  10. ↑ Hutchinson F (September 1966). "The molecular basis for radiation effects on cells". Cancer Research. 26 (9): 2045–52. PMID 5924966.
  11. 1 2 Daly MJ (March 2009). "A new perspective on radiation resistance based on Deinococcus radiodurans". Nature Reviews. Microbiology. 7 (3): 237–45. doi:10.1038/nrmicro2073. PMID 19172147. S2CID 17787568.
  12. ↑ Daly MJ, Gaidamakova EK, Matrosova VY, Kiang JG, Fukumoto R, Lee DY, et al. (September 2010). "Small-molecule antioxidant proteome-shields in Deinococcus radiodurans". PLOS ONE. 5 (9): e12570. Bibcode:2010PLoSO...512570D. doi:10.1371/journal.pone.0012570. PMC 2933237. PMID 20838443.
  13. ↑ Gupta P, Gayen M, Smith JT, Gaidamakova EK, Matrosova VY, Grichenko O, et al. (2016). "MDP: A Deinococcus Mn2+-Decapeptide Complex Protects Mice from Ionizing Radiation". PLOS ONE. 11 (8): e0160575. Bibcode:2016PLoSO..1160575G. doi:10.1371/journal.pone.0160575. PMC 4976947. PMID 27500529.
  14. ↑ Gaidamakova EK, Myles IA, McDaniel DP, Fowler CJ, Valdez PA, Naik S, et al. (July 2012). "Preserving immunogenicity of lethally irradiated viral and bacterial vaccine epitopes using a radio- protective Mn2+-Peptide complex from Deinococcus". Cell Host & Microbe. 12 (1): 117–124. doi:10.1016/j.chom.2012.05.011. PMC 4073300. PMID 22817993.
  15. ↑ Sharma A, Gaidamakova EK, Grichenko O, Matrosova VY, Hoeke V, Klimenkova P, et al. (October 2017). "2+, gauged by paramagnetic resonance". Proceedings of the National Academy of Sciences of the United States of America. 114 (44): E9253–E9260. doi:10.1073/pnas.1713608114. PMC 5676931. PMID 29042516.
  16. ↑ Doble PA, Miklos GL (July 2018). "Distributions of manganese in diverse human cancers provide insights into tumour radioresistance". Metallomics. 10 (9): 1191–1210. doi:10.1039/c8mt00110c. PMID 30027971.
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