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

ionizing radiation Ionizing (ionising) radiation, including Radioactive decay, nuclear radiation, consists of subatomic particles or electromagnetic waves that have enough energy per individual photon or particle to ionization, ionize atoms or molecules by detaching ...

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 The cell cycle, or cell-division cycle, is the sequential series of events that take place in a cell (biology), cell that causes it to divide into two daughter cells. These events include the growth of the cell, duplication of its DNA (DNA re ...

. This is described by the 'law of Bergonié and Tribondeau', formulated in 1906:

X-rays An X-ray (also known in many languages as Röntgen radiation) is a form of high-energy electromagnetic radiation with a wavelength shorter than those of ultraviolet rays and longer than those of gamma rays. Roughly, X-rays have a wavelength ran ...

are more effective on cells which have a greater reproductive activity. 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

erythroblast A nucleated red blood cell (NRBC), also known by #Nomenclature, several other names, is a red blood cell that contains a cell nucleus. Almost all vertebrate organisms have hemoglobin-containing cells in their blood, and with the exception of mamm ...

s, epidermal stem cells, gastrointestinal stem cells. The least sensitive are nerve cells and muscle fibers. Very sensitive cells are also oocytes and

lymphocyte A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include T cells (for cell-mediated and cytotoxic adaptive immunity), B cells (for humoral, antibody-driven adaptive immunity), an ...

s, 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. This has been demonstrated across several cancer types and in normal tissues.

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.

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 Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

is the most important. It develops because radiation causes

DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...

s 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. 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. 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. 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 Manganese is a chemical element; it has Symbol (chemistry), symbol Mn and atomic number 25. It is a hard, brittle, silvery metal, often found in minerals in combination with iron. Manganese was first isolated in the 1770s. It is a transition m ...

ions and small organic metabolites. These complexes were shown to protect the proteins from oxidation ''in vitro'' and also increased radiation survival in mice. 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. 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. 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.

References