Mutagens are the physical, chemical or biological agents that can cause mutation.
Mutagens can be broadly classified as Two Types:
- Endogenous Mutagens
- Exogenous Mutagens
Mutagens are said to endogenous if they are already present inside the body of an organism. One of the most notable examples of endogenous mutagens is Reactive Oxygen Species (ROS).
They are naturally occurring metabolites produced during oxidative phosphorylation in mitochondria. Examples of ROS are superoxides, hydrogen peroxides.
As their name suggests they are highly reactive and reacts with various cell components, including DNA and can cause significant damage to the cell’s genetic code. One way by which they can cause damage to DNA is Double-Strand Break in which DNA is broken down into smaller helix thereby causing the shape of DNA which leads to mutation. The next type of damage which ROS can cause is BASE MODIFICATION: the nucleotide bases are swapped or replaced thereby causing mutation.
Now you may be wondering why cell makes something that can cause damage to it, but the fact is ROS has some beneficial effects and the cell has a certain mechanism so that it doesn’t cause harm, but sometimes ROS becomes too high that the cell can’t deal with it which leads to a condition known as Oxidative Stress.
They can be classified into Three Types:
- Physical Mutagens
- Chemical Mutagens
- Biological Mutagens
They are further classified into two types:
- Ionizing Radiations
- Non-Ionizing Radiations
When ionizing radiation falls on the skin, they can penetrate the tissue, which causes the elimination of electrons from their outer orbit leading to the formation of ions. These ions can break the covalent bond between sugar-phosphate backbone in DNA causing mutation. They are used to kill cancer cells. Examples: X-rays, Cosmic rays, Y-rays, a-rays etc..
When the radiation does not have enough energy to knock down electrons from the outer orbit, then the radiations are said to be non-ionizing. These kinds of radiations generally don’t induce mutation, but an exception to this is UV light.
UV light increases energy in pyrimidine bases of DNA, which leads to the formation of abnormal bonds between adjacent pyrimidine molecules. Normally, base pairing occurs on opposite strands of the DNA helix i.e adenine pairs with thymine and guanine with cytosine, but due to UV rays pairing occurs on the same strand of DNA helix i.e Thymine pairs with Thymine (T=T) leading to the formation of thymine dimer that disturbs DNA replication.
Chemical Mutagens are placed into two groups:
- Those that are mutagenic to both replicating and non-replicating DNA such as nitrous acid.
- Those that are mutagenic to only replicating DNA such as acridine dyes and base analogues.
Base analogues are the molecules having the same structure as DNA bases and they can exist in two conditions either as a normal or rare condition. Let’s take the example of 5-bromouracil (5-BU). Under normal conditions, it exists as Thymine thereby pair with Adenine and in rare conditions behaves as cytosine thereby pairing with Guanine. These base analogues are incorporated into DNA only during replication and once incorporated they cause mispairing and eventually give rise to mutation. Other examples of base analogues are 2-aminopurine, 6-methyl purine etc..
These include acridine dyes, ethidium bromide and proflavin. These agents get incorporated between DNA bases either on one strand or on both the strands. During replication both the strands separate to form a daughter strand. Replication process requires DNA polymers which can recognize only four base pairs (A, T, G, C) so when it comes over intercalating agent it cannot recognize it and adds some random base amongst the four to a daughter strand say it adds adenine. When this daughter strand will undergo replication this adenine will pair with thymine so a new A=T pair develops which was not present in parent DNA leading to mutation.
Note: If an intercalating agent is added on the parent strand it leads to addition mutation and it adds on the daughter strand it leads to deletion mutation.
IT acts by oxidative deamination of A, G, C bases which contain an amino group. Adenine is deaminated to hypoxanthine which pairs with C. Guanine is converted to xanthine which pairs with C. Cytosine is converted to U which pairs with A.
- Human Papilloma Virus
- Hepatitis B virus
- Helicobacter Pylori