Binucleated cells are cells that contain two nuclei. This type of cell is most commonly found in cancer 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 microscopic level. Stains and dyes are frequently used in histology (microscopic study of biological tissues), in cytology (microscopic study of cells), and in the ...

and

microscopy Microscopy is the technical field of using microscopes to view objects and areas of objects that cannot 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 mic ...

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

mitosis In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is maint ...

. 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, ...

s, chondrocytes and in

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

(

dikaryon The dikaryon is a nuclear feature which 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 can fuse cytoplasms ...

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 division. ...

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 division. ...

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 meios ...

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 ...

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 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 in mitosis and meios ...

: The cell can fail to form a cleavage furrow, leading to both nuclei remaining in one cell. *

Multipolar spindles Multipolar spindles are spindle formations characteristic of cancer cells. Spindle formation is mostly conducted by the aster of the centrosome which it forms around itself. In a mitotic cell wherever two asters convene the formation of a spindle ...

: 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, and a ...

, 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 to arrest them wherever they are in the

cell cycle The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and subs ...

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 cytoske ...

must next be made visible so that binucleation can be identified.

DAPI DAPI (pronounced 'DAPPY', /ˈdæpiː/), or 4′,6-diamidino-2-phenylindole, is a fluorescent stain that binds strongly to adenine– thymine-rich regions in DNA. It is used extensively in fluorescence microscopy. As DAPI can pass through an i ...

is a dye that binds to DNA and fluoresces blue. For this reason, it is particularly useful at labeling nuclei.

Antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

probes can be used to label

fluorescently. The

immunofluorescence Immunofluorescence is a technique used for light microscopy with a fluorescence microscope and is used primarily on microbiological samples. This technique uses the specificity of antibodies to their antigen to target fluorescent dyes to speci ...

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 cancer cells. Other identifying features of cancer cells include

multipolar spindles Multipolar spindles are spindle formations characteristic of cancer cells. Spindle formation is mostly conducted by the aster of the centrosome which it forms around itself. In a mitotic cell wherever two asters convene the formation of a spindle ...

micronuclei 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 ...

, 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 portion of the cell cycle that is not accompanied by visible changes under the microscope, and includes the G1, S and G2 phases. During interphase, the cell grows (G1), replicates its DNA (S) and prepares for mitosis (G2). A c ...

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, mitos ...

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 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 ...

disjunction making it much more likely for cells to accumulate

References

External links

{{Authority control Carcinogenesis Oncology Cell cycle Cellular processes Mitosis