Mutagens- Definition, Types (Physical, Chemical, Biological)

A mutagen is a chemical, physical, or biological agent that can change the genetic code in DNA resulting in the alterations of the DNA sequences. Similarly, the alterations in the DNA sequences are known as mutations.

  • Mutations that are caused by any agents are called mutagens.
  • Mutagenicity is the ability of the agents or substances to induce alterations in the bases of the DNA.
  • Physical, chemical, and biological mutagen are different types of mutagens.
  • Some examples of mutagens include radioactive substances, X-rays, ultraviolet rays, tobacco products, alkylating agents, transposons, and a wide variety of chemicals.
  • Mutagens exposure can lead to forming certain kinds of diseases.
  • The hereditary material of the living cell is DNA which is made up of several nitrogen bases along with sugar and phosphorous molecule, and this typical pattern of the nucleic acid bases codes all the genetic information of the cell.
  • When the mutagen is exposed to these nucleic acid bases, then it alters the specific patterns and sequences of nucleic acid bases resulting in the change of protein transcribed by it.
  • The changes that occur due to these mutagens may be inheritable and non-inheritable depending on their occurrence in the somatic cell or germline cell.

Types and examples of mutagens

There are three major categories of mutagens that include:

  • Physical mutagens
  • Heat and radiation
  • Chemical mutagens
  • Base analogs
  • Intercalating agents
  • Metal ions
  • Alkylating agents
  • Biological mutagens
  • Virus 
  • Bacteria
  • Transposons and insertion sequence
Mutagens
Mutagens

Physical agents of mutation

  • Heat: At a temperature above 95 degrees Celsius, DNA is very much sensitive. The phosphodiester bond above this temperature breaks, breaking the DNA strand. Hence, DNA breakage is due to the heat.
  • Radiations: the first agent that was reported mutagenic were radiations which can be both ionizing and non-ionizing radiations like UV rays, X-rays, alpha rays, and neutrons. These all kinds of mutations are found to exert a mutagenic effect. Most of these radiations either kill the cells or change the function of the cell by directly affecting the sequences of the DNA or damaging the nucleotides. The DNA damage may include:
  • Cross-linking of the DNA or Proteins
  • Breaking down the chromosomes
  • DNA strand breakdown and loss of chromosomes

Not only DNA but Proteins and Lipids in the dividing cells are affected by ionizing radiation or high-energy radiation. Because of these radiations, free radical molecules are generated causing the DNA or chromosome breakage. X-rays are generally considered lethal at the dose of 300-500 rems, and this dose causes the breaking of the DNA strand by the breakage of the phosphodiester bonds. Some of the non-ionizing radiations are UV rays that have less energy than X-rays, which are used for the sterilization decontamination process. 

UV radiations are of different types and may result in the dimerization of the pyrimidine and alteration of the DNA. Different health issues may be seen because of the dimerization process.

Chemical agents of mutation

  • Base analogs: 5-Bromouracil and 2-aminopurine are the most common base analog chemical mutagens similar to that of purine and pyrimidines. During the process of replication, these base analogs get incorporated with the DNA base because of the structural similarity. The structure of aminopurine is similar to that of adenine, so it binds with the T.

A tautomeric form is exhibited by the 5-Bromouracil, in which it combines with the base pairs. Thymine in the DNA is replaced by the keto form of 5-Bromouracil and forms the pairing with the adenine, whereas complementary base pairing with the guanine is formed by the enol tautomeric form. Thus these base analogs change the base pairs resulting in the alterations of the DNA sequences.

  • Intercalating agents: intercalating agents are the molecules that resemble the ring structure of base pairs of DNA and these agents have a hydrophobic heterocyclic ring structure. Intercalating agents interfere with the replication, translation, and transcription resulting in the mutation (mostly frameshift mutation) by placing these agents into the DNA helix.

Some of the examples of intercalating agents include Ethidium bromide, proflavine, acridine orange, actinomycin D, and daunorubicin.

  • Metal ions: some of the metal ions generates reactive oxygen species that cause DNA hypermethylation. Some of the mineral ions including nickel, chromium, cobalt, cadmium, arsenic, and iron may promote DNA damage and hinder the process of DNA repair mechanism.
  • Alkylating agents: the alkylating agents results in DNA damage by introducing the alkyl group in the DNA helix which results in the error of the base pairs and induces the gaps in the DNA strand due to increased ionization. Ethylnitrosourea, mustard gas, vinyl chloride, methylhydrazine, Busulfan, Dimethyl sulfate, temozolomide, ethyl ethane sulfate, and thio-TEPA are some of the common alkylating agents. Through the process of depurination (a non-mutagenic process), these agents can be removed from the DNA.

Biological agents of mutation

  • Transposons and insertion sequences: transposons are the units of DNA that relocate or multiply the DNA fragments. The simplest forms of transposons are known as insertion sequences. Both the transposons and insertion sequences can move from and throughout the DNA and are also known as the jumping genes. The functionality of the genes is also interrupted by the transposons. There are three types of transposons that include:
  • Replicative transposons: retains the original locus and translocates its copy.
  • Conservative transposons: during this, the original transposons translocate themselves.
  • Retrotransposons transpose: they translocate through RNA intermediates.
  • Viruses: When the viral DNA is inserted into the genome, its genetic function is disturbed. Viruses can be mutagenic as they have been reported to induce cancer, including the Rous sarcoma virus.
  • Bacteria: certain bacteria are responsible for the production of reactive oxygen species like Helicobacter pylori that damage the DNA and reduce the DNA repair mechanism. Because of this, it leads to mutations.

Effects of the mutagens

Cancer Cell Transformation
Cancer Cell Transformation
  • Mutagens can result in the change of the DNA and hinder the replication and transcription of the DNA. It may also lead to cell death in severe conditions.
  • Some of the powerful mutagens can also lead to chromosomal instability, causing the chromosomes’ breakage.
  • It may also lead to chromosomal rearrangements and breakage such as translocation, deletion, and inversion. Mutagens that bring chromosomal deformities are known as clastogens.
  • Some types of mutagens can change the number of chromosomes in the cell and can also lead to aneuploidy.
  • Cancer may be caused due to the accumulation of mutagens.

References

  1. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/mutagen
  2. https://www.biologyonline.com/dictionary/mutagen
  3. https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/mutagenic-agent
  4. https://www.biologyonline.com/dictionary/mutagen
  5. https://www.genome.gov/genetics-glossary/Mutagen
  6. https://www.iaea.org/projects/crp/d24011
  7. https://pt.slideshare.net/fizzahnaeem/physical-and-chemical-mutagen-copy-36963398/3

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