Mutagens

How many kinds of mutations?
Is it possible for DNA restoration? 

How many kinds of mutations?
There are several types, they are spontaneous mutations, induced mutations, large and point mutations, somatic and germinal mutations.

Spontaneuos mutations
Mutations that occur without the introduction of an exogenous (outside) mutagenic agent. Various types of chemical reaction in the cell may cause these types of mutations. This type of mutation can be caused by the broken of sugar-four bases by chemical intermediates (superoxide, OH radicals, hydrogen peroxide) produced during metabolism, deamination, methylation, some mistakes made by endogenous enzyme in replicating DNA, and some additions or deletions of bases during DNA replication (may occur when there are short complementary base sequences located in the same DNA strand).

Induced mutations
This is associated with the introduction of exogenous chemical agents or physical agents such as radiation into the cell. Mutations occur by these mechanisms: base-analog substitution, base modification and base intercalation.

Base analog mutations occur when a chemical substance similar in chemical structure replaces one of the bases. These chemicals are capable of forming bonds with the normal bases in DNA. 5-bromouracil is similar in structure to thymine. During DNA replication, thymine is replaced by 5-bromouracil, which does not bind with thymine’s normal base pair adenine, rather, 5-bromouracil binds with other bases such as guanine.

Base modifying agents change the structure of DNA by either remove the amino group of the base, or add a hydroxil group, or add a hydrocarbon group to the base (similar with the process of metabolism, instead this involve exogenous agents). Examples of chemicals  are chemotherapeutic agents such as chloroethylnitros-ureas, nitrogen mustards, epoxides and aldehydes.

Intercalating agents are substances that are insertd between the bases in the DNA and form a hydrogen bond with one of the bases. Actinomycin D intercalates between guanin and cytosine (G-C) base pairs and form hydrogen bonds with guanine.

Skin cancer caused by UV radiation is also part of this type of mutation.

Large and Point mutations
The mutation which occur according to the size – large and point – of the DNA segment undergoing mutation. Deletion, inversion and translocation are processes that involve hundreds to thousands of base pairs and several different genes, producing changes in large segments of the DNA. These are called large mutations and have been associated with the development of tumors in somatic cells.

Deletions occur at any point along the chromosome, generally result in fewer bases in a chromosome. This is caused by a break in the DNA strand that is not repaired. Iversion is a chromosomal aberration (deviation) in which a segment of the DNA is inverted 180 degrees. Translocation occurs when segments of DNA are exchanged between different chromosomes, or when segments are transferred to a different part of the same chromosome.

A change in a single base is a point mutation. The substitution of cytosine for thymine, adenine for guanine, or vice versa for either pair, is referred to as a transitional point mutation.

Somatic and germinal mutations 
Mutations may be categorized to their location. If they occur in cells other than the germinal (mula-mula/asal) cells of the reproductive system, they are referred to as somatic mutations. Mutations occuringin the reproductive cells are referred to as germinal mutations.

Is it possible for DNA restoration?
Yes, there are intracellular DNA mechanisms that are able to recognize changes in the DNA molecule and repair them. Two of them are the Base Excision Repair (BER) and the Nucleotide Excision Repair (NER). It is estimated that there are hundreds of genes involved in the synthesis of the enzymes required for recognition and repair of altered DNA. In some cases, mutations of the genes involved in the DNA repair mechanism itself may hinder the repair of altered DNA, allowing mutted genes to survive and affect normal cell functioning.

Reference:
Kent, C. 1998. Basics of Toxicology. John Wiley & Sons, Inc. New York