Explain how a range of mutagens operate, including but not limited to:
- electromagnetic radiation sources
- naturally occurring mutagens
Electromagnetic Radiation Sources:
- A range of radiations such as X-rays, gamma rays, UV rays, alpha particles etc. are categorized as Physical Mutagens.
- Ionizing Radiations (X-rays, gamma rays, alpha particles) operate by:
- Causing breakage of phosphodiester bonds in the sugar-phosphate backbones in DNA.
- Creating breakages in multiple sites causing rearrangement and deletion of nucleotide base pairs in the DNA molecule.
- At times, causing bond breakage in both DNA strands, where the DNA is cut in two places, the middle piece spins round, and is joined back again in the opposite orientation.
- Mode of operation of Non-Ionizing Radiation (UV rays):
- UVA might not possess the energy to cause direct DNA damage but, it can facilitate the formation of free oxygen radicals that can damage other cells and organs of the body.
- UVB causes direct DNA damage by inducing bond formation between consecutive pyrimidines in the same strand of DNA by C=C bonds which is known as Pyrimidine dimers. These dimers cause lesions in the DNA altering the structure and possibility of base-pairing.
- Base Analogues:
- Chemical compounds that have structural similarity with the 4 nitrogen bases in DNA.
- Can replace any of the regular base pairs in DNA.
- Common example is 5-bromo-uracil. Has similar properties with that of thymine when it transitions from its keto form to enol form by shifting hydrogen bonds within the molecule (tautomeric shift) and thus has the capability of replacing thymine in A=T bonds.
- Again, the enol form can infrequently substitute Cytosine as well.
- Nitrous oxides:
- Causes transformation of amine groups into keto groups by oxidative deamination.
- The order of frequency of deamination (removal of amino group) is adenine > cytosine > guanine.
- Deamination of Adenine forms hypoxanthine whose pairing features are similar to that of guanine. Thus, instead of AT bonds, GC bonds are seen in sites where deamination of adenine occurred.
- Deamination of Cytosine results in formation of uracil. The affinity for hydrogen bonding of uracil is like thymine; therefore, C-G pairing is replaced by U-A pairing.
- Deamination of Guanine results in formation of xanthine. Xanthine, more or less behaves like Guanine itself and thus pairs with Cytosine. Thus, mutation in Guanine does not create abnormalities in base pairing.
- Modifies Cytosine by hydroxylation and deamination causing Cytosine to bond with Thymine instead of Guanine.
- Alkylating Agents:
- Causes alkylation in N7 position in Guanine and N3 position in Adenine resulting in mismatch during base pairing.
- Can cause cross-linking and breakage of DNA.
Naturally Occurring Mutagens:
- Are found in surroundings and mostly originate from microbes, plants and animals.
- Some examples include:
- Transposon - A section of DNA that can change its position in genomes altering gene identity in cells and genome size.
- Virus – Virus DNA may be inserted into the genome which can diversify genetic function.
- Bacteria – some bacteria such as Helicobacter pylori cause inflammation during which oxidative species are produced, causing DNA damage and reducing efficiency of DNA repair systems, thereby increasing mutation.
Extract from HSC Biology Stage 6 Syllabus. © 2017 Board of Studies NSW.