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Mutagen: Definition, Types, Nature, Effects

Mutagen: Definition, Types,  Effects, and Nature

Mutagens: Definition, Types Effects and Nature

Mutagen Definition:

  • Mutagens are the biological, chemical, or physical agents that can change the DNA sequence.

  • Any factor that can promote the mutation in organisms is called a mutagen.

  • Any substance that can cause a sudden or fundamental change in the genetic material of an organism, making gene mutation or chromosomal aberration above the natural level, is collectively referred to as a mutagen.

What is Mutagens?
  • A mutagen is a biological,  chemical, or physical agent that can change the DNA sequence.
  • When energy or mutagenic agents are transferred into the living body through radiation or other substances, various molecules in the living body are ionized and excited, and then many chemically active free atoms or free radicals are generated. 
  • They continue to react with each other and their surrounding substances, especially macromolecular nucleic acids and proteins, causing changes in molecular structure. 
  • This in turn affects some biochemical processes in the cell, such as the suspension of DNA synthesis, changes in various enzyme activities, etc., and further profound changes in the structure of each part, of which the most important is chromosomal damage. 
  • Changes in the structure and number of chromosomes due to chromosomal breakage and reconnection are called chromosomal mutations. In contrast, changes in bases in the structure of DNA molecules result in gene mutations. 
  • Those cells with chromosomal mutations or gene mutations can produce a genetic variation of organisms by passing the mutated genetic material to sex cells or asexual reproductive organs through cell generations.
  • There are three main categories of mutagens: biological mutagens, physical mutagens, and chemical mutagens. 
  • Commonly used biological mutagens are viruses, bacterial toxins, etc.
  • Commonly used physical mutagens include ultraviolet rays, x-rays, gamma rays (such as Co60, etc.), alpha rays, beta rays, and ultrasonic waves. 
  • Commonly used chemical mutagens are base analogs, alkylating agents, hydroxylamines, acridine compounds, etc.

What is mutation?

  • A mutation is defined as a sudden change in the sequence of DNA.
  • The causes of mutations remained unclear for a long time. 
  • For the first time, artificial mutations were obtained in 1925 by Soviet scientist Georgy Adamovich NAdson and his colleagues by irradiating yeast fungi with X-rays, and 
  • In 1927, the American geneticist Herman Muller caused directed mutations by exposing Drosophila to X-rays.
  • Mutations are caused by chance or by mutagenic agents called mutagens.
  • Mutagens may be chemicals, biological, physical, and radiation. 
  • The mutation is of two types genetic mutation and chromosomal mutation. 
  • When the change involves a small number of bases, then the mutation is genetic. 
  • When it is associated with changes in a larger part of the chromosome, it is called a chromosomal abnormality/Mutation. 
  • The mutations contribute to the creation of genetic diversity in the population and are responsible for many inherited diseases, as well as for many cases of cancer. 
  • Mutations can occur in any germ or body cell of an organism. 
  • Only germ cell mutations, however, can be passed from one generation to the next. But that does not mean that bodily mutations are less important for health. 
  • In fact, they are the majority of mutations, since an adult organism consists of about 1013 somatic cells.

History of Mutagens:
  • For the first time, artificial mutations were obtained in 1925 by Soviet scientist Georgy Adamovich NAdson and his colleagues by irradiating yeast fungi with X-rays, and 
  • In 1927, the American geneticist Herman Muller caused directed mutations by exposing Drosophila to X-rays.
  • At the beginning of the 20th century, physical mutagens were discovered. Radiation is the best known among them. 
  • In the 1930s, T. Morgan used the effect of ionizing radiation in experiments with Drosophila. 
  • At the same time, chemical mutagenesis was discovered, and domestic scientists stood at the origins of this discovery. 
  • So, geneticists V.V. Sakharov and M.E. Lobashev showed that under the influence of chemical compounds (iodine, acetic acid, ammonia) the frequency of mutations in the cells of the buckwheat plant increases. 
  • Later I.A. Rapoport (USSR) and S. Auerbach (Great Britain) discovered powerful chemical mutagens, which they called supermutagens.
  • Currently, environmental and drug mutagens are often added to physical, chemical, and biological mutagens.

Nature of mutagens:
  • Mutagens are usually chemical compounds or ionizing radiation and can be divided into different categories according to their effect on DNA replication.
  • Some mutagens act as base analogs and insert into the DNA strand during replication instead of the substrates.
  • Some react with DNA causing structural changes that lead to miscopying of the sequence in the chain when the DNA is replicated.
  • Others do it indirectly by causing cells to synthesize chemicals that have a direct mutagenic effect.

Types and Examples of Mutagens:

There are many different mutagens in nature. Under their influence, various mutations constantly occur in organisms. Mutagens are most often classified according to the nature of the influencing factors. There are physical, chemical, and biological mutagenic factors. Mutagens are also divided into groups according to their origin - spontaneous and induced. Spontaneous mutagens act under normal natural conditions for no apparent reason, while induced mutagens are specially used by humans to initiate mutations. However, in both spontaneous and induced mutagenesis, either the physical, chemical or biological properties of mutagens act as active principles. Following are the important mutagens.
  1. Biological Mutagens.
  2. Physical Mutagens. 
  3. Chemical Mutagens. 

1. Biological Mutagens
Biological mutagens are the living things that alter or change the genetic material of the host organism. Examples of biological mutagens include viruses, bacteria, and transposons.
  • Viruses: Viruses are biological mutagens. Studies have shown that in cells affected by viruses, mutations occur much more often than in healthy ones. Viruses introduce a certain amount of their own genetic information into the genotype of the host cell, changing it and causing it to produce mutations.
  • Bacteria: Some bacteria act as a biological mutagenic agent such as Helicobacter pylori can increase the risk of developing stomach cancer.
  • Transposons:  A transposable element is a mobile DNA sequence in the genome that can "jump" from one location in the genome to another location. Transposable elements are also known as transposons, jumping genes. These elements are found in many metazoans, including nematodes, insects, Plants, and humans. Because transposable elements can not only bring new genetic material to the genome, but also turn on or off certain genes like a switch in some cases, and often cause DNA rearrangements such as deletion, duplication, or inversion in the genome

2. Physical Mutagens
Physical mutagens include Heat, ultraviolet (UV), χ-ray, γ-ray, laser and ultrasonic wave, etc. Among various physical mutagenic factors, radiation is the most widely used and effective. Radiation used for mutagenesis includes ionizing radiation and non-ionizing radiation.

1. Radiation
Radiation includes ionizing radiation and non-ionizing radiation. 

Ionizing radiation:
  • Ionizing radiation includes alpha rays, beta rays, gamma rays, X rays, neutrons, etc. 
  • When energy is transferred into the living body through radiation, various molecules in the living body are ionized and excited, and then many chemically active free atoms or free radicals are generated.
  • They continue to react with each other and their surrounding substances, especially macromolecular nucleic acids and proteins, causing changes in molecular structure.

Non-ionizing Radiation
  • Ultraviolet rays, visible light, and Infrared is a kind of non-ionizing radiation, which can make the inner electrons in the molecules or atoms of the irradiated substances increase the energy level to transition to the outer orbits with high energy ( called excitation), resulting in physicochemical changes in the molecule. 
  • Base pairs on DNA molecules strongly absorb UV light, and pyrimidines are 100 times more sensitive than purines. 
  • Ultraviolet radiation can cause DNA strand breaks, intra- and intermolecular cross-linking of DNA, and cross-linking of nucleic acids and proteins.

2. Heat
  • Heat: Heat is another example of physical mutagens 
  • The helical structure of double-stranded DNA is destabilized by increasing temperature. 
  • Above a critical temperature (the melting temperature), the two strands in duplex DNA become fully separated. 
  • The phosphodiester bond above this temperature breaks, breaking the DNA strand.

3. Chemical Mutagens:
In 1928, the Soviet microbiologist Maxim Nikolaevich Meisel published the results of studies that proved the possibility of obtaining mutations when cells are exposed to chemical compounds. Many chemical mutagens are known today. For example, the alkaloid colchicine destroys the spindle, which leads to a doubling of the number of chromosomes in the cell. Mustard gas, used to make chemical weapons, increases the mutation rate by 90 times. Mutations in the human body can be caused by alcohol, narcotics, and certain drugs.

The main chemical mutagens are:

1. Alkylating agents
  • It is the most important class of mutagens that induce mutations.
  • These substances contain one or more active alkyl groups that can be transferred to molecules with higher electron density, replacing hydrogen atoms in other molecules to change the base. 
  • Alkylating agents affect the transcription of mRNA, thereby disturbing the expression of the protein, making protein recombination, and changing its properties. 
  • The clinical application of such substances as anticancer drugs has a strong killing effect on cancer cells
  • Commonly used are ethyl methanesulfonate (EMS), ethyleneimine (EI), nitrosoethylurethane (NEU), nitrosomethylurethane (NMU), diethyl sulfate (DES), etc.

2. Nucleic acid base analogs
  • The molecular structure is similar to bases, resulting in mismatches during DNA replication, mRNA transcription disorders, functional protein reorganization, and phenotypic changes. 
  • Such substances are relatively less toxic but have a high rate of negative mutagenesis, and it is often difficult to obtain good mutants.
  • As a component of DNA, it penetrates into DNA molecules, causing pairing errors during DNA replication, thereby causing organism variation.
  • Commonly used are 5-bromouracil (BU), 5-bromodeoxyuridine (BudR) and 6-bromouracil, 6-BudR, maleic hydrazide, 2-aminopurine, etc.
  • 5-Bromouracil (BU), and 5-bromodeoxyuridine (BudR) are analogs of thymine (T)
  • 2-Aminopurine (AP) is an analog of adenine (A)
  • Maleic hydrazide (MH) is an isomer of uracil (U).

4. Other mutagens:
  • Nitrous acid (HNO2):  can deaminate purines or pyrimidines, change the structure and properties of nucleic acids, and cause DNA replication disorders. HNO2 can also cause cross-linking between DNA double strands and cause genetic effects.
  • Sodium azide (NaN3): is a respiratory depressant that can cause gene mutation, with high mutation frequency and no residual toxicity.
  • Alkaloids: such as vinblastine, colchicine, camptothecin, etc.
  • Inorganic compounds: relatively easy to obtain, general effect, less dangerous eg. Lithium chloride.
  • Intercalating agent: It is a commonly used type in molecular biology and has a high induction rate. The principle is that such molecules are just the right size to intercalate into base molecules, leading to mismatches. Most commonly used: ethidium bromide (EtBr).
  • Other most commonly used chemical mutagens are nitrogen mustard, ethylene oxide, actinomycin K, hydroxylamine, etc.
  • Drugs: There are also commonly used drugs such as hydrogen peroxide and formaldehyde, which also have certain mutagenic effects. 
  • Antibiotics: Such as diazoserine, mitotoxin C, etc., can damage DNA and nucleic acids, which can cause chromosome breakage.

Effects of Mutagens
  • Mutagens are any physical, chemical, and biological substances that alter or change the genetic material of an organism, hence they are termed genotoxic. 
  • Most of the mutagens are carcinogenic in nature. They can cause cancer.
  • Mutagens can also lead to chromosomal aberration, and cause increased or decreased chromosome numbers.
  • High mutagenic effects may lead to chromosomal rearrangements and breakage such as deletion, inversion, or translocation of chromosomes.
  • High mutation by mutagens leads to cell death in severe conditions.
  • Mutagens can disturb the central dogma process- replication, transcription, and translation by changing the DNA sequence.
  • Mutagens can cause different types of mutations that result in the loss of function, altered function, or formation of non-functional protein.
  • Many mutations cause no visible effect, either because they occur in introns (non-coding DNA) or because they do not change the sequence of amino acids due to codon redundancy.
  • Other mutations cause visible effects and can cause a lethal effect on the host.

Frequently Asked Questions on Mutagens

1. How to use mutagen?
Answer: Mutagens are very harmful to the human body and have a certain carcinogenic effect. When operating, be strictly protected and do not let the agent get on the skin. Used tools should also be strictly collected and isolated to prevent mistakes.

2. What is mutagenesis?
Answer: Mutagenesis refers to the use of physical and chemical factors to induce changes in the genetic characteristics of microorganisms or plants, then select an individual that meets certain requirements of people from the mutant population, and then cultivate new varieties or germplasms.

3. Why UV light mutagenic cultures are kept in the dark?
Answer: Ultraviolet mutagenic microorganisms must be cultured in the dark because bacteria repair pyrimidine dimers formed by UV irradiation in the presence of light, This is called the "photoreactivation" phenomenon.

4. What are mutagens examples?
Answer: Examples of mutagens include radioactive substances, x-rays, ultraviolet radiation, and many chemicals and biological such as bacteria, viruses, and transposons.

5. What are the three types of mutagens?
Answer: Three types of Mutagens are – Physical, Chemical, and Biological Mutagenic Agents.

6. What are the most common chemical mutagens?
Answer: The most commonly used chemical mutagens are alkylating agents such as ethyl methane sulfonate and N-methyl-N-nitrosourea that induce point mutations in DNA.

7. What diseases do mutagens cause?
Answer: Mutagenic agents, which can cause mutations in DNA, pose a serious risk to human health. They can cause serious disorders such as various types of cancer, aging, and neurodegenerative diseases like Alzheimer's.

8. Is UV light a mutagen?
Answer: Yes, Ultraviolet (UV) light induces specific mutations in DNA.

9. How do you detect mutations?
Answer: To detect mutation various detection methods are used such as Protein Truncation Test (PTT), Nucleotide sequencing, Denaturing Gradient Gel Electrophoresis (DGGE), DNA microarray technology, etc.

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