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8. Definere mutagener og carcinogener og forklare hvordan mutationer kan induceres af kemikalier, bestråling, polymerase felj og interkalering i DNA helix.
Devlin, s.192-194
Stryer, s. 768-770

Mutagen – An agent, such as a chemical, ultraviolet light, or a radioactive element, that can induce or increase the frequency of mutation in an organism.

Carcinogen – substance that raises the incidence of cancer. They can be direct carcinogens or procarcinogens. Procarcinogens in their native form do not damage DNA, but they can be activated by metabolitic processes into carcinogens and damage DNA.  
All direct carcinogen substances are also mutagens, but all mutagens are not carcinogens.  

Mutations are changes in the DNA sequence. They can result from:

1. replication error

2. damage to the DNA

3. errors during repair of the damage

Point mutations – change in the single base pair.

There are several types of mutations:

• Substitution – one base pair is substituted with another. It can be a transition, in which one purine is substituted for another or one pyrimidine is substituted for another. It can also be a transversion, where a purine is substituted for a pyrimidine or vice versa.

• Deletition – of one or more base pairs

• Insertion – of one or more base pairs.

• Triplet expansion – a great increase in the number of repeating triplets. It number tends to become bigger from one generation to another. Can be seen in Huntington disease.

Chemical agents can induce mutations by chemically modifying the DNA.

Fx. HNO₂ reacts with bases containing an amino group. Treatment of DNA with HNO₂ results in the conversion of adenine to hypoxanthine. Hypoxanthine pairs with cytosine, inducing a transition from A-T to C-G after the replication.

Ultraviolet light can also act as a mutagen. The ultraviolet component of sunlight is a ubiquitous DNA-damaging agent. Its major effect is to covalently link adjacent pyrimidine residues along a DNA-strand. Such a pyrimidine dimer can not fit into a double helix and so replication and gene expression are blocked until the lesion is removed.  

X-rays are also powerful mutagens. They cause jonisation of the base pairs, so that:

• Instead of A-T, we have A* - G – transversion. (T, pyrimidine is replaced with G, purine)

• Instead of T-A, we have T* - G – transition. (A, purine is replaced with G, purine)

• No mutation, in the case of C* - G.

X-rays produce also double stranded breaks at any stage of the cell cycle in a dose-dependant linear fashion. 
 

Mutations can also be induced by substances that can intercalate in the DNA-helix. They are flat aromatic molecules that slip in between adjacent base pairs in the DNA double helix. That way DNA polymerase can introduce extra base pairs (which make hydrogen bonds with the intercalated molecules) on the daughter strand. They shift the reading frame in translation.

DNA polymerase can also make mistakes, even though it has proofreading and initial selection activity. Because of these two properties, the error rate is reduced to 10 ^{– 9}. So, there are still mutations. That is why repair systems are needed. 

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