6.1.1 Mutagens Flashcards
Mutagens
Definition
Substances or processes that can dramatically increase the rate of mutations, often beyond what an organism can tolerate
Mutagenesis
Definition
The process of inducing mutation, and the resulting mutations are termed as induced mutations
Radiation
Types of Mutagens: Physical Mutagens
UV rays, X-rays, gamma radiation and sometimes beta radiation all have the potential to damage DNA and other organic molecules by disrupting their bonds, which can lead to a change in its functioning.
This can be lethal or sub-lethal by causing:
- base deletions
- single nicks in DNA strands
- cross-linking or chromosomal breaks
The severity of the damage depends on the dose and frequency. For example, short term exposure can lead to a condition called acute radiation syndrome (ARS) or radiation sickness.
Long exposure to UV radiation can cause pyrimidine dimers to form, otherwise known as skin cancer.
Photoreactivation
Repairing Pyrimidine Dimers
Directly undoes the damage done by UV light by using the enzyme photolyase, which is activated by visible light, to absorb the photon of light and break the covalent bond between the thymine bases.
Nucleotide Excision Repair
Repairing Pyrimidine Dimers
An incision is made on either side of the lesion to entirely remove it from the strand so that DNA polymerase can then be used to repair the gap using the code on the complementary strand and DNA ligase to bond it.
Non-Ionizing Radiaton
Types of Mutagens: Physical Mutagens
There is little evidence to suggest that the lower frequency and energy of radio waves, microwaves and alpha radiation cause any damage to DNA.
Intercalating Agents
Types of Mutagens: Chemical Mutagens
Chemicals that insert themselves into the bonds between base pairs and alter the shape of the DNA, leading to errors in replication.
For example, ethidium bromide is used as a laboratory stain to visualise DNA and proflavine is used as a bacterial disinfectant. Any replication with these mutagens may contain:
- single-nucleotide additions
- deletions.
Base Analogues
Types of Mutagens: Chemical Mutagens
Chemicals that are structurally similar to nitrogenous bases and can be incorporated into the DNA sequence during replication. This means that the DNA can no longer function, leading to a change in the amino acid sequence and protein functioning.
For example, 5BrU (5-bromouracil) is an analogue of thymine and can substitute for it.
DNA Reactive Chemicals
Types of Mutagens: Chemical Mutagens
Chemicals that react directly with DNA and can cause:
- bond breakages
- cross-links
For example, reactive oxygen species (ROS)
Tobacco
Types of Mutagens: Chemical Mutagens
Contains mutagenic substances, some of which are carcinogenic for cancers of the lung, pharynx and larynx.
In Australia, smoking is responsible for 84% of new lung cancers in males and 77% in women.
Heavy Metals
Types of Mutagens: Chemical/Naturally-Occurring Mutagens
Some heavy metals such as arsenic and cadmium are chemical mutagens that occur naturally in the environment, but it is not understood how these damage DNA.
Virus
Types of Mutagen: Biological Mutagens
Common mutagens that are well-known to us and create lethal health issues. They insert their DNA into our genome, disrupting its functioning and replicating into a viral protein in place of our own protein.
Bacteria
Types of Mutagen: Biological Mutagens
Some bacteria are dangerous for our DNA, provoking DNA damage and breakage.
Transposon
Types of Mutagen: Biological Mutagens
Also known as transposable elements, they are non-coding DNA sequences that jump from one place to another in a genome to influence the function of genes.
Proto-oncogenes
Disrupting the Cell Cycle
Mutations can cause changes to the genes called proto-oncogenes, which monitor the regulation of cell division and cell death to stop, leading to uncontrolled cell division.
Tumour-Suppressor Genes
Disrupting the Cell Cycle
Exist to slow cell division and repair DNA, so if these mutate, uncontrolled cell division can result.
Cancer
Mutagen Case Study
Cancer can be the result of a mutagen that causes uncontrolled cell division that leads to a neoplasm (tumour). Neoplasms are either:
- Benign - localised masses that do not turn into cancer
- Potentially Malignant - localised masses that will eventually spread to turn into cancer
- Malignant - masses that invade other tissues and transform into cancer