Radiation mutagenesis

Mutations are caused by DNA damage and genetic alterations that may occur spontaneously at a very low rate. The frequency of these mutations can be increased by using special agents called mutagens. Ionizing radiation was the first mutagen that efficiently and reproducibly induced mutations in a multicellular organism. Direct damage to the cell nucleus is believed to be responsible for both mutations and other radiation mediated genotoxic effects like chromosomal aberrations and lethality. Free radicals generated by irradiation of the cytoplasm are also believed to induce gene mutations even in the non-irradiated nucleus.

There are many kinds of radiations that can increase mutations. Radiation is often classified as ionizing or non-ionizing depending on whether ions are emitted in the penetrated tissues or not. X rays, gamma rays (γ), beta particle radiation ([.beta]), and alpha particle ([.alpha]) radiation (also known as alpha rays) are ionizing form of radiation. On the other hand, UV radiation, like that in sunlight, is non-ionizing. Biologically, the differences between types of radiation effects fundamentally involve the way energy is distributed in irradiated cell populations and tissues. With alpha radiation, ionizations lead to an intense but more superficial and localized deposition of energy. Primary ionization in x rays or gamma radiation traverses deeper into tissues. This penetration leads to a more even distribution of energy as opposed to the more concentrated or localized alpha rays.

This principle has been used experimentally to deliver radiation to specific cellular components. A cumulative effect of radiation has been observed in animal models. This means that if a population is repeatedly exposed to radiation, a higher frequency of mutations is observed that is due to additive effect. Intensive efforts to determine the mutagenic risk of low dose exposure to ionizing radiation have been an ongoing concern because of the use of nuclear energy and especially because of the exposure to radon gas in some indoor environments. Radon is estimated by the United States Environmental Protection Agency to be the cause of more than 20,000 cases of lung cancer annually.

The relative efficiencies of the different types of radiations in producing mutations is assessed as the mutagenic effect. The mutagenic effect of radiation is generally assumed to be due to direct damage to DNA, but the identity of the specific lesions remains uncertain.

Investigation of radiation's mutagenic effects on different tissues, cells, and subcellular compartments is becoming possible by the availability of techniques and tools that allow the precise delivery of small doses of radiation and that provide better monitoring of effects. Reactive oxygen species released in irradiated cells are believed to act directly on nuclear DNA and indirectly by modifying bases that will be incorporated in DNA, or deactivating DNA repair enzymes . Novel microbeam alpha irradiation techniques have allowed researchers to investigate radiation-induced mutations in nonirradiated DNA. There is evidence that radiation induces changes in the cytosol that—in eukaryotes—are transmitted to the nucleus and even to neighboring cells. Direct measurement of DNA damage caused by ionizing radiation is performed by examining micronucleus formation or analysis of DNA fragments on agarose gels following treatment with specific endonucleases such as those that only cleave at certain sites. The polymerase chain reaction (PCR ) is also used to detect the loss of some marker genes by large deletions. The effect of ionizing radiation on cells can also be measured by evaluating the expression level of the stress inducible p21 protein.

Critical lesions leading to mutations or killing of a cell include induction of DNA strand breaks, damaged bases, and production of abasic sites (where a single base is deleted), and—in multichromosomal organisms—large chromosomal deletions. Except for large deletions, most of these lesions can be repaired to a certain extent, and the lethal and mutagenic effect of radiation is assumed to result principally from incompletely or incorrectly repaired DNA. This view is supported by experimental studies which showed that mice given a single radiation dose, called acute dose, develop a significantly higher level of mutations than mice given the same dose of radiation over a period of weeks or months. The rapid activation of the DNA-repair pathway through p53 protein and the stress-inducible p21 protein as well as the extreme sensitivity of cells with genetic defects in DNA repair machinery support the view that the ability of the cell to repair irradiation-induced DNA damage is a limiting factor in deciding the extent of the mutagenic effects.

See also Evolution and evolutionary mechanisms; Evolutionary origin of bacteria and viruses; Immunogenetics; Molecular biology and molecular genetics; Phage genetics; Radiation resistant bacteria; Radioisotopes and their uses; Viral genetics