Importance of Mitosis, Stem Cells and Cancer

AS · 16 min

Mitosis produces two daughter cells that are genetically identical to each other and to the parent cell. That single property is why mitosis is used for growth, for replacing worn-out cells, for repairing damaged tissue and for asexual reproduction. This note explains each of these, the part played by stem cells, and what happens when the control of mitosis breaks down and cells divide without limit, forming a tumour. Questions are mostly "explain the importance of" and "explain how" questions, where precise wording earns the marks.

Why the daughter cells are genetically identical

Two features of the cell cycle guarantee that the daughter cells have exactly the same genetic information as the parent:

In S phase, each DNA molecule is replicated semi-conservatively with complementary base pairing, so the two sister chromatids of each chromosome are identical copies.
In mitosis, the sister chromatids of every chromosome are separated and one goes to each pole, so each new nucleus receives one copy of every chromosome: the same number and the same genes and alleles as the parent nucleus.

So mitosis is used whenever an organism needs new cells that are the same as existing ones. (Meiosis, by contrast, halves the chromosome number and produces genetically different cells for sexual reproduction; it is an A Level topic.)

Key result

Mitosis produces genetically identical daughter cells, which is important for:

growth of multicellular organisms;
replacement of damaged or dead cells;
repair of tissues by cell replacement;
asexual reproduction.

Growth

A human begins as one cell, the zygote, and grows into an adult of around $3.7 \times 10^{13}$ cells. Every one of those cells was produced by mitosis, so every body cell contains the same genetic information as the zygote. This matters because cells need a complete and identical set of genes to function and to be coordinated with one another, even though different cells use (express) different genes when they differentiate into specialised cells.

In plants, growth by mitosis is concentrated in meristems: the root tip and shoot tip (apical meristems, causing growth in length) and the cambium (causing growth in width). That is why root tips are used to study mitosis.

Replacement of damaged or dead cells

Many cells have short lives and must be replaced constantly:

Red blood cells live about 120 days. They have no nucleus and cannot divide, so they are replaced by cells made by mitosis of stem cells in the bone marrow.
Epithelial cells lining the small intestine are worn away by the movement of food and are replaced every few days by mitosis of stem cells in the crypts between the villi.
Skin cells are lost continuously from the surface and replaced by mitosis in the lowest layer of the epidermis.

The replacement cells must be genetically identical so that they can carry out exactly the same functions as the cells they replace.

Repair of tissues

When tissue is damaged, for example by a cut, a broken bone or damage to the liver, cells next to the damaged area divide by mitosis to produce new cells that fill the gap. Because the new cells are identical to the surrounding cells, they can differentiate into the same cell types and restore the tissue's structure and function. Some tissues, like liver, repair very well; others, such as heart muscle and nervous tissue, have very limited ability to repair.

Asexual reproduction

In asexual reproduction, a single parent produces offspring without gametes. The offspring are produced by mitosis, so they are genetically identical to the parent and to each other: they are clones.

Single-celled eukaryotes such as Amoeba divide by mitosis followed by cytokinesis; yeast reproduces by budding.
Hydra (a small freshwater animal) forms buds that grow into new individuals.
Many plants reproduce asexually by vegetative propagation: strawberry runners, potato tubers, bulbs (e.g. onions), and cuttings taken by gardeners.

Asexual reproduction is fast and needs only one parent, and offspring inherit a combination of alleles that is already successful in that environment. The disadvantage is a lack of genetic variation, so a population may be wiped out by a new disease or a change in the environment.

Watch out

Bacteria divide by binary fission, which is not mitosis: prokaryotes have no nucleus, no linear chromosomes with histones, and no spindle. Do not use bacteria as an example of asexual reproduction by mitosis.

Explaining the importance of mitosis (routine, 4 marks)

Explain why it is important that the cells produced by mitosis are genetically identical, using two examples.

Solution

Cells produced for growth contain the same genes as all other body cells / the zygote, so all cells have a complete set of the organism's genes and can be coordinated.
Cells produced for replacement (e.g. of red blood cells, gut epithelium) or repair (e.g. skin after a wound) must be identical so they can carry out the same function as the cells they replace / differentiate into the same cell type.
In asexual reproduction, offspring are identical (clones) to a parent that is well adapted to its environment.
Identical cells are produced because DNA is replicated exactly (S phase) and sister chromatids are separated so each daughter cell receives one copy of every chromosome.

(Two examples, each explained, plus the reason they are identical.)

Replacing red blood cells (moderate)

An adult has about $2.5 \times 10^{13}$ red blood cells, each with a lifespan of about 120 days.

(a) Calculate how many red blood cells must be produced per second to replace those that die. Give your answer in standard form to two significant figures. (b) Explain why red blood cells cannot replace themselves, and state where they are made.

Solution

(a) Seconds in 120 days $= 120 \times 24 \times 60 \times 60 = 1.0368 \times 10^{7}\ \text{s}$ .

\text{rate} = \frac{2.5 \times 10^{13}}{1.0368 \times 10^{7}} = 2.4 \times 10^{6}\ \text{cells per second}

(b) Mature red blood cells have no nucleus (no DNA or chromosomes), so they cannot carry out mitosis. They are made by mitosis of stem cells in the bone marrow; the new cells then differentiate (losing their nucleus) into red blood cells.

Stem cells

Definition

A stem cell is a cell that can divide an unlimited number of times by mitosis. When it divides, each new cell has the potential either to remain a stem cell or to differentiate into a specialised cell (such as a red blood cell or a muscle cell).

The two properties together, self-renewal and the ability to differentiate, make stem cells the source of new cells for growth, replacement and repair. When a stem cell divides by mitosis, one daughter cell usually stays a stem cell (so the supply never runs out) and the other goes on to divide further and differentiate.

Stem cells differ in how many cell types they can become, which is called their potency:

Type	Can differentiate into	Example
Totipotent	any cell type, including the cells of the placenta	the zygote and cells of the very early embryo (first few divisions)
Pluripotent	almost any cell type in the body (but not placenta)	embryonic stem cells, in the inner cell mass of the early embryo (blastocyst)
Multipotent	a limited range of related cell types	adult stem cells, e.g. bone marrow stem cells that produce all types of blood cell

Stem cells in replacement and repair

In adults, multipotent stem cells in tissues such as bone marrow, the skin, the gut lining and the liver divide by mitosis whenever cells need replacing:

Bone marrow stem cells produce red blood cells, all types of white blood cell and platelets.
Stem cells in the base of the epidermis produce new skin cells.
Stem cells in the intestinal crypts replace the epithelial cells of the villi.

Because stem cells divide many times, they make telomerase, which maintains their telomeres (see Chromosomes and the cell cycle).

Medical uses. Bone marrow transplants are used to treat leukaemia (a cancer of white blood cells): the patient's bone marrow is destroyed by chemotherapy or radiotherapy, and stem cells from a matched donor are transplanted to restore blood cell production. Research aims to use stem cells to repair tissues that cannot repair themselves, such as damaged heart muscle or spinal cord.

In plants, meristem cells behave as stem cells, which is why plants can regenerate whole new plants from cuttings.

Stem cells and leukaemia (moderate, 4 marks)

Explain why a transplant of bone marrow stem cells can restore a patient's supply of blood cells after treatment for leukaemia.

Solution

Stem cells can divide by mitosis an unlimited number of times / are self-renewing, so a small number of transplanted cells can produce a continuous supply of new cells for the rest of the patient's life.
Each division produces cells that can remain stem cells or differentiate.
Bone marrow stem cells are multipotent: they can differentiate into all types of blood cell (red blood cells, white blood cells and platelets).
The new cells are genetically identical to the donor's stem cells (healthy, without the cancer mutations), so they function normally.

Cancer: uncontrolled cell division

How mitosis is normally controlled

In a healthy tissue, the rate of mitosis is tightly controlled so that the number of new cells exactly balances the number lost. The cell cycle has checkpoints (at the end of G1, at the end of G2 and during metaphase) where the cell checks, for example, that its DNA is undamaged and has been fully replicated before it continues. Two groups of genes are involved:

Proto-oncogenes code for proteins that stimulate cell division, such as receptors for growth factors.
Tumour suppressor genes code for proteins that inhibit cell division, or that stop the cycle when DNA is damaged and trigger apoptosis (programmed cell death) if the damage cannot be repaired.

Normal cells also stop dividing when they touch neighbouring cells (contact inhibition) and stop dividing after a limited number of divisions (telomere shortening).

How a tumour forms

Key result

Uncontrolled cell division and tumours

A mutation (change in the base sequence of DNA) occurs in a gene that controls the cell cycle, for example in a proto-oncogene (which becomes an oncogene, permanently "switched on") or in a tumour suppressor gene (which is "switched off").
The protein coded for by the gene is altered or not produced, so the cell no longer responds to the signals that normally control division.
The cell divides repeatedly by mitosis, without control, and does not undergo apoptosis.
All its daughter cells inherit the mutation, so they also divide uncontrollably.
This produces a mass of abnormal cells called a tumour.
Usually several mutations must accumulate in the same cell before it becomes cancerous, which is why most cancers are more common in older people.

A tumour is a mass of cells formed by uncontrolled mitosis. Tumours are of two types:

Benign tumour	Malignant tumour (cancer)
grows slowly	often grows rapidly
cells stay together, often enclosed in a capsule	cells are not enclosed; can invade surrounding tissues
does not spread to other parts of the body	cells can break off and spread through the blood or lymph to form secondary tumours elsewhere (metastasis)
cells usually look like normal, differentiated cells	cells often look abnormal and unspecialised, with large nuclei
can usually be removed by surgery; can still be harmful if it presses on organs	harder to treat; life-threatening

Cancer is the name for diseases caused by malignant tumours. Cancer cells typically also produce telomerase (so they divide indefinitely) and stimulate the growth of blood vessels into the tumour to supply oxygen and nutrients.

Carcinogens

Any factor that increases the chance of mutation increases the risk of cancer. Such factors are called carcinogens. Examples:

ionising radiation (X-rays, gamma rays, radiation from radon gas) and ultraviolet light (sunlight; skin cancer);
chemicals such as the tar in tobacco smoke (lung cancer), asbestos fibres, and some food contaminants;
some viruses, such as human papillomavirus (HPV), which can cause cervical cancer;
inherited mutations in some genes (e.g. BRCA1 and BRCA2) increase the risk of particular cancers.

Many cancer treatments, such as chemotherapy drugs and radiotherapy, act by disrupting DNA replication or mitosis, which affects rapidly dividing cells most. This is why they also damage other rapidly dividing cells, such as hair follicles, gut lining and bone marrow, causing side effects.

Tumour growth (moderate)

A tumour starts from a single cell. Its cells divide on average every 60 days, and none die.

(a) Calculate how many doublings are needed for the tumour to reach about $1 \times 10^{9}$ cells (roughly the size at which it can first be detected). (b) Calculate how long this would take, in years. (c) Suggest why tumours often grow much more slowly than this calculation predicts.

Solution

(a) After $n$ doublings there are $2^{n}$ cells. $2^{30} = 1.07 \times 10^{9}$ , so 30 doublings (more precisely, $n = \log_2(10^9) = 29.9$ ).

(b) $30 \times 60 = 1800\ \text{days} = 1800 / 365 = 4.9\ \text{years}$ .

(c) Not all tumour cells divide: some die (e.g. those far from blood vessels, short of oxygen and nutrients); some are killed by the immune system; some cells stop dividing; the cell cycle time varies. So the net doubling time is longer.

Exam-hard: how a tumour forms (6 marks)

Explain how uncontrolled cell division can result in the formation of a tumour, and why a malignant tumour is more dangerous than a benign one.

Solution

A mutation / change in the base sequence of DNA occurs, e.g. caused by a carcinogen (UV, ionising radiation, chemicals in tobacco smoke);
in a gene that controls the cell cycle / mitosis, e.g. a proto-oncogene becomes an oncogene or a tumour suppressor gene is inactivated;
so the cell divides by mitosis repeatedly / uncontrollably, ignoring signals to stop; it does not undergo apoptosis;
the daughter cells inherit the mutation and also divide uncontrollably, forming a mass of cells = tumour.
A malignant tumour can invade surrounding tissues and cells can break off and travel in the blood or lymph to form secondary tumours elsewhere (metastasis);
a benign tumour stays in one place (often in a capsule) and does not spread, so it can usually be removed completely by surgery.

Watch out

"Cancer is caused by cells dividing too much" is not an explanation. Say why: a mutation in a gene that controls cell division, leading to uncontrolled mitosis.
A tumour is formed by mitosis, not meiosis. Cancer cells still divide by mitosis; it is the control that has failed.
Not all tumours are cancers: benign tumours do not spread.
A stem cell is defined by unlimited division and the ability to differentiate. "A cell that is not specialised" alone is not enough.
Bacteria do not divide by mitosis.

Exam tip

The syllabus lists four roles of mitosis: growth, replacement of damaged or dead cells, repair of tissues by cell replacement, asexual reproduction. Learn an example for each and link it to genetically identical cells.
In stem cell questions, the key phrases are: "divide by mitosis an unlimited number of times", "can differentiate into specialised cells", and "one daughter cell remains a stem cell".
For tumours, examiners expect: mutation → gene controlling cell cycle → uncontrolled mitosis → mass of cells (tumour). For extra marks: proto-oncogene/oncogene, tumour suppressor gene, carcinogen, metastasis, apoptosis.
Do not write long essays on cancer treatment unless asked; the syllabus focuses on how tumours form.

Summary

Mitosis produces genetically identical daughter cells because DNA is replicated exactly and sister chromatids are separated equally.
Mitosis is used for growth, replacement of damaged or dead cells, repair of tissues, and asexual reproduction.
Stem cells divide by mitosis an unlimited number of times; each new cell can remain a stem cell or differentiate.
Totipotent (zygote), pluripotent (embryonic), multipotent (adult, e.g. bone marrow) stem cells.
Stem cells in bone marrow, skin and gut replace cells continuously; bone marrow transplants restore blood cell production.
Mutations in genes controlling the cell cycle (proto-oncogenes, tumour suppressor genes) cause uncontrolled mitosis, forming a tumour.
Benign tumours do not spread; malignant tumours invade and spread (metastasis) and are cancers.
Carcinogens (UV, ionising radiation, tobacco chemicals, some viruses) increase the chance of mutation.

Practice questions

Question

State four roles of mitosis in multicellular organisms.
Explain why the two cells produced by mitosis are genetically identical. (2 marks)
Give two examples of asexual reproduction by mitosis.
Define the term stem cell.
Distinguish between totipotent, pluripotent and multipotent stem cells.
State two differences between a benign tumour and a malignant tumour.
Explain what is meant by a carcinogen and give two examples.
The lining of the human small intestine has a surface area of about $30\ \text{m}^2$ and its epithelial cells are replaced every 4 days. Suggest why a high rate of mitosis is needed in this tissue, and why chemotherapy often causes digestive problems. (3 marks)
Explain why a mutation in a single body cell can result in a tumour containing millions of cells. (4 marks)
Scientists can take skin cells from a patient and reprogramme them into pluripotent stem cells. (a) Suggest why these cells could be used to replace damaged heart muscle. (b) Suggest one advantage of using the patient's own cells rather than cells from a donor. (c) Suggest one risk of using stem cells that can divide an unlimited number of times. (6 marks)

Answers

Growth; replacement of damaged or dead cells; repair of tissues (by cell replacement); asexual reproduction.
DNA is replicated (semi-conservatively) in S phase, producing identical sister chromatids; in mitosis sister chromatids are separated, so each daughter nucleus receives one copy of each chromosome / the same number and type of chromosomes as the parent.
Any two: budding in yeast or Hydra; division of Amoeba; vegetative propagation in plants such as runners (strawberry), tubers (potato), bulbs, cuttings.
A cell that can divide (by mitosis) an unlimited number of times, where each new cell can either remain a stem cell or differentiate into a specialised cell.
Totipotent cells can differentiate into any cell type, including placental cells (e.g. zygote); pluripotent cells can form almost any cell type of the body but not placenta (embryonic stem cells); multipotent cells can form only a limited range of related cell types (e.g. bone marrow stem cells form blood cells).
Any two: benign does not spread / malignant spreads (metastasis) via blood or lymph; benign often encapsulated / malignant invades surrounding tissue; benign usually slower growing; benign cells resemble normal differentiated cells, malignant cells often abnormal/undifferentiated.
A factor that increases the chance of mutation (in DNA) and so increases the risk of cancer. Examples (any two): UV light; ionising radiation such as X-rays or gamma rays; tar/chemicals in tobacco smoke; asbestos; some viruses such as HPV.
Epithelial cells are continually worn away/damaged by food passing and must be replaced quickly to maintain the large surface area for absorption; mitosis of stem cells (in the crypts) provides genetically identical replacement cells. Chemotherapy drugs target rapidly dividing cells (by interfering with DNA replication or mitosis), so they also stop replacement of gut epithelial cells, which leads to damage of the gut lining and digestive problems.
The mutation is in a gene controlling the cell cycle (e.g. proto-oncogene → oncogene, or tumour suppressor gene inactivated); the cell divides by mitosis without control / does not undergo apoptosis; all daughter cells inherit the mutated gene (mitosis produces genetically identical cells); so they also divide uncontrollably; repeated doubling rapidly produces millions of cells (e.g. 20 doublings gives over a million).
(a) Pluripotent cells can divide by mitosis to produce many cells and can differentiate into almost any cell type, including cardiac muscle cells; heart muscle cells themselves rarely divide, so damaged heart muscle cannot repair itself. (b) The cells are genetically identical to the patient's own cells, with the same antigens, so they are not recognised as non-self and not rejected by the immune system (no need for immunosuppressant drugs); no donor needed. (c) Cells that divide without limit could continue dividing uncontrollably after transplant and form a tumour; or they might differentiate into the wrong cell type.

Why the daughter cells are genetically identical

Growth

Replacement of damaged or dead cells

Repair of tissues

Asexual reproduction

Stem cells

Stem cells in replacement and repair

Cancer: uncontrolled cell division

How mitosis is normally controlled

How a tumour forms

Carcinogens

Practice questions

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