Binucleated cells are cells that contain two nuclei. This type of cell is most commonly found in

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

cells and may arise from a variety of causes. Binucleation can be easily visualized through

staining Staining is a technique used to enhance contrast in samples, generally at the Microscope, microscopic level. Stains and dyes are frequently used in histology (microscopic study of biological tissue (biology), tissues), in cytology (microscopic ...

and

microscopy Microscopy is the technical field of using microscopes to view subjects too small to be seen with the naked eye (objects that are not within the resolution range of the normal eye). There are three well-known branches of microscopy: optical mic ...

. In general, binucleation has negative effects on cell viability and subsequent

mitosis Mitosis () is a part of the cell cycle in eukaryote, eukaryotic cells in which replicated chromosomes are separated into two new Cell nucleus, nuclei. Cell division by mitosis is an equational division which gives rise to genetically identic ...

. They also occur physiologically in

hepatocyte A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass. These cells are involved in: * Protein synthesis * Protein storage * Transformation of carbohydrates * Synthesis of cholesterol, bi ...

chondrocyte Chondrocytes (, ) are the only cells found in healthy cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteoglycans. Although the word '' chondroblast'' is commonly used to describe an immatu ...

s and in

fungi A fungus (: fungi , , , or ; or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and mold (fungus), molds, as well as the more familiar mushrooms. These organisms are classified as one ...

(

dikaryon The dikaryon (karyogamy) is a cell nucleus feature that is unique to certain fungi. (The green alga '' Derbesia'' had been long considered an exception, until the heterokaryotic hypothesis was challenged by later studies.) Compatible cell-types c ...

Causes

Cleavage furrow In cell biology, the cleavage furrow is the indentation of the cell's surface that begins the progression of cleavage, by which animal and some algal cells undergo cytokinesis, the final splitting of the membrane, in the process of cell divisio ...

regression: Cells divide and almost complete division but then the

cleavage furrow In cell biology, the cleavage furrow is the indentation of the cell's surface that begins the progression of cleavage, by which animal and some algal cells undergo cytokinesis, the final splitting of the membrane, in the process of cell divisio ...

begins to regress and the cells merge. This is thought to be caused by

nondisjunction Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate properly during cell division (mitosis/meiosis). There are three forms of nondisjunction: failure of a pair of homologous chromosomes to separate in meiosis I ...

chromosomes A chromosome is a package of DNA containing part or all of the genetic material of an organism. In most chromosomes, the very long thin DNA fibers are coated with nucleosome-forming packaging proteins; in eukaryotic cells, the most importa ...

but the mechanism by which it occurs is not well understood. Cleavage Furrow Regression

* Failed

cytokinesis Cytokinesis () is the part of the cell division process and part of mitosis during which the cytoplasm of a single eukaryotic cell divides into two daughter cells. Cytoplasmic division begins during or after the late stages of nuclear division ...

: The cell can fail to form a cleavage furrow, leading to both nuclei remaining in one cell. * Multipolar spindles: Cells contain three or more

centrioles In cell biology a centriole is a cylindrical organelle composed mainly of a protein called tubulin. Centrioles are found in most eukaryotic cells, but are not present in conifers ( Pinophyta), flowering plants ( angiosperms) and most fungi, an ...

, resulting in multiple poles. This leads to the cells pulling

in many directions that end in multiple nuclei found in one cell. * Merging of newly formed cells: Two cells that have just finished

merge into one another. This process is not entirely understood.

Medical relevance

Detection

Binucleated cells can be observed using

. Cells must first be

fixed Fixed may refer to: * ''Fixed'' (EP), EP by Nine Inch Nails * ''Fixed'' (film), an upcoming animated film directed by Genndy Tartakovsky * Fixed (typeface), a collection of monospace bitmap fonts that is distributed with the X Window System * Fi ...

to arrest them wherever they are in the

cell cycle The cell cycle, or cell-division cycle, is the sequential series of events that take place in a cell (biology), cell that causes it to divide into two daughter cells. These events include the growth of the cell, duplication of its DNA (DNA re ...

and to keep their structures from degrading. Their nuclei and

tubulin Tubulin in molecular biology can refer either to the tubulin protein superfamily of globular proteins, or one of the member proteins of that superfamily. α- and β-tubulins polymerize into microtubules, a major component of the eukaryotic cytosk ...

must next be made visible so that binucleation can be identified. DAPI is a dye that binds to

DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...

and fluoresces blue. For this reason, it is particularly useful at labeling nuclei.

Antibody An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as pathogenic bacteria, bacteria and viruses, includin ...

probes can be used to label

fluorescently. The

immunofluorescence Immunofluorescence (IF) is a light microscopy-based technique that allows detection and localization of a wide variety of target biomolecules within a cell or tissue at a quantitative level. The technique utilizes the binding specificity of anti ...

may then be observed with

. Binucleated cells are most easily identified by viewing

, which surrounds the two nuclei in the cell. Binucleated cells may be mistaken for two cells in close proximity when viewing only nuclei.

Cancer

Binucleation occurs at a much higher rate in

cells. Other identifying features of

cells include multipolar spindles,

micronuclei A micronucleus is a small cell nucleus, 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 inst ...

, and chromatin bridge. However, the increased rate of binucleation is usually not high enough to make it a conclusive diagnostic tool.

Effects

The fate of binucleated cells depends largely on the type of cell they originated from. A large percentage of binucleated cells arising from normal cells remain in

interphase Interphase is the active portion of the cell cycle that includes the G1, S, and G2 phases, where the cell grows, replicates its DNA, and prepares for mitosis, respectively. Interphase was formerly called the "resting phase," but the cell i ...

and never enter

again. Cells that contain many

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, mitosi ...

before they become binucleate are much more likely to proceed through subsequent rounds of mitosis. One study found that more than 50% of binucleated cells never entered mitosis again while greater than 95% of cancer cells were able to proceed through mitosis. Subsequent rounds of mitosis in binucleated cells have much higher rates of errors in

chromosomal A chromosome is a package of DNA containing part or all of the genetic material of an organism. In most chromosomes, the very long thin DNA fibers are coated with nucleosome-forming packaging proteins; in eukaryotic cells, the most importa ...

disjunction making it much more likely for cells to accumulate

References

External links

{{Authority control Carcinogenesis Oncology Cell cycle Cellular processes Mitosis