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 The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and subs ...

of the

cell cycle The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and sub ...

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

X-rays An X-ray, or, much less commonly, X-radiation, is a penetrating form of high-energy electromagnetic radiation. Most X-rays have a wavelength ranging from 10 picometers to 10 nanometers, corresponding to frequencies in the range 30&nbs ...

are more effective on cells which have a greater reproductive activity. From their observations, they concluded that quickly dividing

tumor cell A neoplasm () is a type of abnormal and excessive growth of tissue (biology), tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tiss ...

s are generally more sensitive than the majority of body cells. This is not always true. Tumor cells can be

hypoxic Hypoxia means a lower than normal level of oxygen, and may refer to: Reduced or insufficient oxygen * Hypoxia (environmental), abnormally low oxygen content of the specific environment * Hypoxia (medical), abnormally low level of oxygen in the t ...

and therefore less sensitive to X-rays because most of their effects are mediated by the

free radical A daughter category of ''Ageing'', this category deals only with the biological aspects of ageing. Ageing Ailments of unknown cause Biogerontology Biological processes Causes of death Cellular processes Gerontology Life extension Metabo ...

s 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 A spermatogonium (plural: ''spermatogonia'') is an undifferentiated male germ cell. Spermatogonia undergo spermatogenesis to form mature spermatozoa in the seminiferous tubules of the testis. There are three subtypes of spermatogonia in humans: ...

and

erythroblast A nucleated red blood cell (NRBC), also known by 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 mammals, all of t ...

s, epidermal stem cells, gastrointestinal stem cells. The least sensitive are

nerve cell A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. No ...

s and

muscle fiber A muscle cell is also known as a myocyte when referring to either a cardiac muscle cell (cardiomyocyte), or a smooth muscle cell as these are both small cells. A skeletal muscle cell is long and threadlike with many nuclei and is called a muscl ...

s. Very sensitive cells are also

oocyte An oocyte (, ), oöcyte, or ovocyte is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is produced in a female fetus in the ovary during female gametogenesis. The femal ...

s and

lymphocyte A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic ad ...

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 The International Commission on Radiological Protection (ICRP) is an independent, international, non-governmental organization, with the mission to protect people, animals, and the environment from the harmful effects of ionising radiation. Its r ...

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 abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

is the most important. It develops because radiation causes DNA

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 replication, DNA or viral repl ...

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 In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of molecular oxygen () p ...

(ROS), which are the main mechanism of radiation toxicity, is played by non-enzymatic complexes of

manganese Manganese is a chemical element with the symbol Mn and atomic number 25. It is a hard, brittle, silvery metal, often found in minerals in combination with iron. Manganese is a transition metal with a multifaceted array of industrial alloy use ...

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 Immunogenicity is the ability of a foreign substance, such as an antigen, to provoke an immune response in the body of a human or other animal. It may be wanted or unwanted: * Wanted immunogenicity typically relates to vaccines, where the injectio ...

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 Electron paramagnetic resonance (EPR) or electron spin resonance (ESR) spectroscopy is a method for studying materials that have unpaired electrons. The basic concepts of EPR are analogous to those of nuclear magnetic resonance (NMR), but the spi ...

) 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