Cancerous Micronuclei
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Cancerous micronuclei is a type of
micronucleus Micronucleus is the name given to the small nucleus that forms whenever a chromosome or a fragment of a chromosome is not incorporated into one of the daughter nuclei during cell division. It usually is a sign of genotoxic events and chromosomal i ...
that is associated with cancerous cells.


History

Theodor Boveri Theodor Heinrich Boveri (12 October 1862 – 15 October 1915) was a German zoologist, comparative anatomist and co-founder of modern cytology. He was notable for the first hypothesis regarding cellular processes that cause cancer, and for describ ...
originally observed the fact that abnormal nuclear morphologies commonly occur in
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
. Micronuclei are also referred to Howell-Jolly bodies; discovered by hematologists
William Henry Howell William Henry Howell (February 20, 1860 – February 6, 1945) was an American physiologist. He pioneered the use of heparin as a blood anti-coagulant. Early life William Henry Howell was born on February 20, 1860, in Baltimore, Maryland. He gra ...
and
Justin Marie Jolly Justin Marie Jolly (August 6, 1870 – February 1, 1953) was a French hematologist and histologist born in Melun, Seine-et-Marne. He was a pioneer in the field of hematology as it pertained to the study of living tissue. He studied medicine at ...
in erythrocytes. Micronucleus induction by a chemical was first reported in Ehrlich ascites
tumor cells A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
treated with colchicine. The effect of environmental stressors on the expression of micronuclei was first analyzed in root tip cells under
ionizing radiation Ionizing radiation (or ionising radiation), including nuclear radiation, consists of subatomic particles or electromagnetic waves that have sufficient energy to ionize atoms or molecules by detaching electrons from them. Some particles can travel ...
. It can be inferred that nuclear abnormalities are a result of various molecular mechanisms. These events can ultimately lead to
cell death Cell death is the event of a biological cell ceasing to carry out its functions. This may be the result of the natural process of old cells dying and being replaced by new ones, as in programmed cell death, or may result from factors such as dis ...
.


Description


Characteristics

Micronuclei are characterized in the cells that have some sort of DNA damage. This includes damage caused by
radiation In physics, radiation is the emission or transmission of energy in the form of waves or particles through space or through a material medium. This includes: * ''electromagnetic radiation'', such as radio waves, microwaves, infrared, visi ...
, harmful
chemicals A chemical substance is a form of matter having constant chemical composition and characteristic properties. Some references add that chemical substance cannot be separated into its constituent elements by physical separation methods, i.e., wit ...
, and random
mutations In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...
that occur throughout the
genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...
. Micronuclei are small bodies that can be seen budding off of a newly divided daughter cell. Micronuclei can contain a whole
chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...
or part of a
chromatid A chromatid (Greek ''khrōmat-'' 'color' + ''-id'') is one half of a duplicated chromosome. Before replication, one chromosome is composed of one DNA molecule. In replication, the DNA molecule is copied, and the two molecules are known as chro ...
. The increased formation of micronuclei is usually an indication of increased DNA damage or
mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...
. It is characteristically found in
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
cells, or cells that have been exposed to increased risk factors.


Formation

Micronuclei are small, extranuclear bodies that are formed during mitosis from lagging
chromosomes A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...
. In
anaphase Anaphase () is the stage of mitosis after the process of metaphase, when replicated chromosomes are split and the newly-copied chromosomes (daughter chromatids) are moved to opposite poles of the cell. Chromosomes also reach their overall maxim ...
, the
microtubules Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27  nm and have an inner diameter between 11 an ...
are not attached properly to the chromosomes, which can cause pulling in a different direction. This results in parts of the
chromatids A chromatid (Greek ''khrōmat-'' 'color' + ''-id'') is one half of a duplicated chromosome. Before replication, one chromosome is composed of one DNA molecule. In replication, the DNA molecule is copied, and the two molecules are known as chro ...
or
chromosomes A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...
being broken off and enveloped as an extra
nucleus Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to: *Atomic nucleus, the very dense central region of an atom *Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA Nucle ...
in one of the daughter cells. This is the main way that micronuclei are formed. Micronuclei can also be spontaneously formed as a byproduct of cellular defense. If the cell senses extra
chromosomes A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...
, the cell can attempt to remove the extra
chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...
in another
cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
, separate from the other normal
chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...
. Another mechanism to micronuclei formation is by a double-strand break in the DNA, creating a separate linear fragment. Furthermore, the breaking of an
anaphase bridge Chromatin bridge is a mitotic occurrence that forms when telomeres of sister chromatids fuse together and fail to completely segregate into their respective daughter cells. Because this event is most prevalent during anaphase, the term anaphase br ...
could also lead to formation of a micronucleus. The formation of an abnormal nuclear structure called
chromosome bridge A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...
also predisposes to micronucleation. Bridges arise from end-to-end chromosome fusions after DNA breakage or telomere crisis, incomplete DNA replication, or failed resolution of chromosome catenation.


Role in cancer

Micronuclei are often overlooked in
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
diagnosis and treatment. If observed, they are viewable under a
microscope A microscope () is a laboratory instrument used to examine objects that are too small to be seen by the naked eye. Microscopy is the science of investigating small objects and structures using a microscope. Microscopic means being invisibl ...
and often located next to other larger nuclei. Based on the structure of a Micronucleus, or the function of a cell, it seems to provide support in the central apparatus within the cell. Micronuclei are under investigation and research regarding whether or not they can be used to predict future cancer risks. It seems that they are easy to analyze compared to ''
chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...
aberrations''.


References

* Chang P, Li Y, Li D (2010) Micronuclei levels in peripheral blood lymphocytes as a potential biomarker for pancreatic cancer risk. {{doi, 10.1093/carcin/bgq24 * Fenech M, Kirsch-Volders M, Natarajan AT, Surrales J, Croft J, Parry J, Norppa H (2011) Molecular mechanisms of micronucleus, nucleoplasmic bridge and nuclear bud formation in human cells. * Iarmarcovai G, Ceppi M, Botta A, Orsie`re T, Bonassi S (2008) Micronuclei frequency in peripheral blood lymphocytes of cancer patients: a meta-analysis. Mutat Res 659:274–283 * Terradas M, Mart ́ın M, Tusell L, Genesca` A (2009) DNA lesions sequestered in micronuclei induce a local defective-damage response. DNA Repair 8:1225–1234 Oncology