Mutagens

In simple language, we will say that mutagens are the agents that damage our genetic material, usually DNA, and result in genetic abnormalities– either inherited or non-inherited. This role is played by mutagenic agents. As per mutagenic agents' definition, the process describes monitoring and measuring the mutagenic potential of agents, which involves creating it. Using transgenic non-human organisms, DNA is inspected for spontaneous induced mutations to 1 or more suspected mutagenic agents. Some of the most common mutagenic agents examples are UV light, X- rays, ROS, alkylating agents and base analogy, etc.

Carcinogen, compounds that have been related to cancer, were the first mutagen to be discovered. Hermann Joseph Muller first discovered the mutagenic properties of mutagens while performing experiments on fruit flies in the year 1927. He observed that the exposure to X-rays can result in genetic mutations in the fruit flies.  

Types of Mutagens

Three different types of common mutagens are observed in nature- physical and chemical mutagens agents and biological agents.

• Physical Agents: It includes high energy radiations such as gamma rays, X- rays and alpha particles and increase in temperature.

• Chemical Agents: They are of various types such as nitrous acid, alkylating agents, acridines, and base analogues.

• Biological Agents: It includes viruses, bacteria, and transposons.

Physical Mutagenic Agents

• High Energy Radiation

High energy radiations are the primary mutagenic agent reported in 1927. UV rays, X-rays, alpha rays, neutrons, and other ionising and non-ionizing radiations are mutagenic. Usually, radiation directly damages the DNA or nucleotide structure, which could be either lethal or sub-lethal. The electromagnetic wave is additionally one in every of the known mutagens that cause harmful or sub-lethal mutations. Not even the DNA but also proteins and lipids present in an exceeding cell. The rapidly dividing cells are a chief target for ionising radiations like X-rays. 

• Temperature

Temperature is another mutagen that provokes mutations in our DNA. The rise in temperature results in the breakage of hydrogen bonds present in the DNA and it becomes denatured- two single-stranded DNA. Also, extreme heat damages DNA and breaks the phosphodiester bonds too.

Chemical Mutagenic Agents

• Base Analogs

The base analogs are chemicals like the bases of DNA- purine, and pyrimidines or structurally resemble the DNA bases. Bromouracil and aminopurine are two common base analogs incorporated into DNA- rather than usual bases, during the method of replication. The 5-bromouracil are artificially synthesized molecules- a base analog utilized within the genetic research which is incorporated in DNA in situ of the thymine. Rather than the methyl of the thymine, the bromouracil contains Br group- highly resembles the thymine.

• Alkylating Agents

Ethyl nitrosourea, poison gas, diethyl sulphate (DES), dimethyl nitrosamine(DMN), methylhydrazine, temozolomide, dacarbazine, busulfan, Ethyl ethane sulfate (EMS) and vinyl chloride are common alkylating agents that add alkyl radical to the DNA and damages it. These agents result in ethylation or methylation of nitrogen bases and induce base-pairing errors by increasing ionization and producing gaps within the DNA strand. The alkylated purine bases are removed by the phenomenon called depurination, although depurination isn't mutagenic. It might be repaired by the DNA repair pathway. 

Intercalating Agents

The EtBr- ethidium bromide used during the agarose gel electrophoresis is one in every one of the intercalating agents. Other intercalating agents like proflavine, acridine orange, or daunorubicin operated by an identical mechanism like the EtBr.  The molecules intercalate between the bases of DNA and disrupt its structure. If it's incorporated during the replication, it can cause frameshift mutation. It's also going to block transcription.

• Metal Ions

Metal ions are also dangerous to our DNA because it acts in styles of other ways. Nickel, chromium, cobalt, cadmium, arsenic, chromium, and iron are a number of the standard metal ions that cause mutations. The metal ions work by producing ROS (reactive oxygen species), hindering the DNA repair pathway, causing DNA hypermethylation, or may directly damage the DNA.

• Other Chemical Mutagens

Reactive oxygen species, benzene, gum elastic and rubber products, sodium azide, aromatic amines, alkaloids, deaminating agents, and PAH (Polycyclic aromatic hydrocarbons) are other mutagens that make different mutations.

Biological Mutagenic Agents 

• Virus

We all fathom HIV, right! A causative agent of AIDS. Infections are common mutagens that are well-known to us and create lethal health issues. Viruses insert their DNA into our genome and disrupt the traditional function of DNA or genes. Once it inserts DNA, the DNA replicates, transcribes, and translates viral protein rather than our protein. Mature viral particles form in an exceeding cell.

• Bacteria

Some bacteria also are dangerous for our DNA- cause inflammation. It provokes DNA damage and DNA breakage.

• Transposons

Lesser-known biological mutagens are transposons. The transposons are non-coding DNA sequences, jump from one place to a different place in an exceedingly large genome, and influence the function of genes.

Mutagenic Effect

The mutagens are genotoxic- harmful to our DNA in some ways; some directly affect the DNA some indirectly. And thus, the precise effect of every mutagen remains unknown to us. At the chromosomal level, the mutagens can alter the structure or number of chromosomes. As deletion, insertion, duplication, translocation, monosomy, and nondisjunction are a number of the chromosomal abnormalities produced by mutagens. The mutagens also affect or dysregulate the molecular central dogma process- replication, transcription, and translation. At the molecular level, the mutagens create different gene mutations that end up in the loss of function, altered function, or non-functional protein.