1. Continuity of Life
The life cycle of humans and flowering plants consists of alternating diploid and haploid stages which is necessary for growth and sexual reproduction.
2. What is Ploidy Level
Ploidy is a term referring to the number of sets of chromosomes within the nucleus of the cell. Diploid cells are those with 2 sets of chromosomes in the nucleus. Human beings, most animals and many plants are diploid organisms since all the cells in the body are diploid except their gametes. We abbreviate diploid as 2n. Haploid cells have only one set of chromosome which is abbreviated as n. These cells are also called the gametes or sex cells. Organisms with more than 2 sets of chromosomes are termed as polyploidy.
3. Types of Cell Division
To achieve the diploid and haploid stages in the life cycle of humans, animals and higher plants, 2 different mechanisms of cell division are required. Cell division consists of 2 stages. Nuclear division is the process of separating nuclear DNA to daughter cells and can occur in either mitosis or meiosis. Cytoplasmic division is the process of separating cytoplasm to daughter cells. The type of cell division is named after the process of nuclear division a cell undergoes.
Mitosis is the process involving 1 nuclear division. It produces 2 genetically identical diploid daughter cells (no variation). It maintains the cell’s original ploidy level. It produces somatic or vegetative cell lines and occurs in most organs in the human body.
Meiosis is a process involving 2 nuclear divisions. It produces 4 genetically non-identical haploid daughter cells or gametes. Each daughter cell contains half the number of chromosomes of the parent cell. It is a reductive cell division. It produces gametes or germ line cells and occurs in the gonads.
4. Significance of Mitosis
It ensures genetic stability as the cell replicates. There is no variation in genetic information due to the absence of crossing over and exchange of DNA between homologous chromosomes. There is no variation in chromosome number or ploidy level due to semi-conservative DNA replication and equal distribution of DNA. New daughter cells contain the full set of chromosomes and identical hereditary information of the parent cell.
The number of cells within an organism increases by mitosis and this is the basis of growth in multicellular organisms which originates from a single diploid zygote.
Cells in the skin, vaginal and oesophageal lining are constantly shed off, dying and being replaced by new ones. When damaged tissues are repaired, the new cells must be exact copies of the cells being replaced so as to retain the normal cell functions.
Some animals are able to regenerate whole parts of the body.
Mitosis is the basis of asexual reproduction, the production of new individuals of a species by one parent organism. Since the offspring produced are identical to the parents, the offspring have all the advantages of the parents in maximizing the resource in the same habitat as long as the environment does not change. These offspring are often described as clones.
5. The Cell Cycle
It is defined as the period from the formation of a cell by division to the point that the cell itself divides. It is the sequence of growth, DNA replication, growth and cell division that all cells go through.
6. Interphase
Most cells are observed in interphase, the longest part of the cell cycle. Interphase is not a resting phase, but a period during which the metabolic activity of the nucleus is very intense. After cytokinesis of the pervious division, the daughter cells are quite small and low on ATP. They acquire ATP and increase in size during the first growth phase (G1 of interphase). After that, the cells then undergo DNA syntheses and this occurs during S phase of interphase. Since the formation of new DNA is an energy draining process, the cells undergoes a second growth and energy acquisition stage (G2 of interphase). This energy is later used in nuclear division.
In interphase, DNA is in the form of very loosely coiled threads called chromatin. Centrioles have replicated. Nucleolus is still present and the nuclear envelope is still intact.
In non-dividing cells, the genetic material in the nucleus is in dispersed phase. DNA appears as lone thin threads, uncoiled and decondensed chromatin. When the cells are primed to undergo mitosis or meiosis, genetic material in the nucleus begins to condense into very distinct chromosomes. The cell is now transciptionally inactive as protein synthesis is temporarily suspended as the cell prepares for nuclear division.
7. Late Interphase to Early Prophase
Analysis of chromosomes in eukaryotic cells has shown them to be composed of DNA and protein, with small amounts of chromosomal RNA. The DNA has negative charges along its length and positively charged protein molecules called histones are bonded to it. This DNA-protein complex is called chromatin.
The large amount of DNA in cells means that there is a packaging problem. The human cell contains abut 2.2 m of DNA distributed among 46 chromosomes. Each chromosome therefore contains about 4.8 cm of DNA. Human chromosomes are on the average about 6 microns long, a packing ratio of 8000:1. In order to maintain a high degree of organization when he DNA is folded, the histone proteins forms a precise architectural scaffolding for the DNA.
It has been shown that the DNA helix combines with groups of 8 histone molecules to form structures known as nucleosomes. These nucleosomes, and the DNA strands linking them, are packed closely together to produce a 30 nm diameter helix with about 6 nucleosomes per turn. This is the 30 nm fibre. It has the packing ratio about 40:1.
Since the DNA must be even more tightly packed than this, the solenoids themselves must be further folded or coiled around other protein framework or scaffold in some way.
8. Morphology of Chromosomes
Metacentric chromosomes have a central centromere and arms of equal length. Submetacentric chromosomes have a submedian centromere and one longer and one shorter arm. Acrocentric chromosomes have centromere very close to one end. Their arms are very unequal in length. Telocentric chromosomes have a terminal centromere and only one arm.
9. Prophase
Sister chromatids are a product of semi-conservative DNA replication during interphase. They are 2 genetically identical chromosomes held together at the centromere during late prophase. Each chromatid is a super coiled DNA double helix.
Centromere consists of a short sequence of about 10 DNA bases which are repeated several thousand times. They are never transcribed into RNA. Centromeres are associated with kinetohores for attachment of spindle fibres. They are concerned with chromosome alignment in meiosis it is the last place to separate in cell division.
10. Stages of Mitosis
10.1 Prophase
Long thin threads of chromatin progressively shorten and condense by a process of supercoiling. The nuclear envelope disintegrates into small vesicles which disperse. The nucleolus gradually disappears. Centrioles migrate to opposite poles in pairs in the cell. They are absent in plants. Short microtubules are seen radiating from the centrioles and these are called asters. The spindle fibres begin to assemble.
10.2 Metaphase
Shortening and thickening of the chromosomes are at its maximum. The 2 sister chromatids and the centromeres are clearly visible. The chromosomes migrate and align singly at the equatorial plate of the spindle. No pairing of homologous chromosomes.
10.3 Anaphase
It begins with the separation of the centromeres. Chromosomes are pulled to the opposite poles of the spindle. Separated daughter chromosomes are pulled along behind he centromeres. This is he shortest stage in mitosis.
10.4 Telophase
It begins when the chromosomes reach the poles of their respective spindles. The nuclear envelope reforms. The chromosomes uncoil into chromatin form. The nucleolus reforms. The 2 nuclei take on the granular appearance of interphase. The spindle fibres disassemble.
10.5 Cytokinesis
This is the process of splitting the daughter cells apart. It is the splitting of the cytoplasm and the allocation of the organelles into each new cell. In preparation for division, the cell organelles become evenly distributed toward the 2 poles of the telophase cell along with the chromosomes.
Where there was one cell, there are now 2 smaller cells each with exactly the same genetic information. These cells may then develop into different adult forms via the processes of development and differentiating.
11. Types of Spindle Fibres
Astral spindle fibres radiate from the centriole towards the peripheral regions of the cells. They are only present in cells that contain centrioles. They serve as a brace for the functioning of the spindle fibres.
Centromeric / kinetochore spindle fibres are fibres attached to the kinetochore of the centromere of the chromatids. They pull the chromatids towards the ends of the spindle during anaphase.
Polar spindle fibres are fibres running from pole to pole overlapping at the equator of the spindle. They are responsible for elongating the whole cell along the polar axis during anaphase.
12. Role of Spindle Fibres
Separation of chromatids may be caused by the following 2 methods.
Shortening of centromeric fibres. Based on subunit disassembly / depolymerization model which suggests that microtubule subunit disassembles / depolymerizes progressively at their polar ends. The shortening of spindle these fibres by the removal of the tubulin subunits account for the movement of chromosomes / chromatids towards the poles.
Elongation of bipolar spindle fibres (pole-to-pole). Based on the sliding filament hypothesis which suggests that the overlapping bipolar fibres slide apart from one another with the aid of motor proteins pushing the spindle poles apart. Simultaneous lengthening / polymerization of bipolar spindle fibres may be occurring by adding subunits removed from centromeric / kinetochore spindle fibres.
13. Rate of Mitotic Cell Cycle
Within a single organism, cells of different tissues have cell cycles of very different durations. Cells lining the small intestine have very short lives and need to be replaced constantly. The cells which divide to replace them do so every 10 hours. Cells of mammalian bone marrow may divide every 8-10 hours to produce new blood cells. Liver cells retain but do not normally utilize their capacity for division. They do not divide at all, unless tissue around them is damaged or if part of he liver is removed, in which case, they may enter a cell cycle and divide rapidly until the liver reaches its former size. Most types of cells never divide again after they have grown and become specialized.
In plants, the majority of cells in roots, stems and leaves never divide. Cell division is only carried out by groups of cells in regions known as meristems. Their cell division is seasonal. The length of the cell cycle depends upon external factors such as temperature and supply of nutrients.
14. Regulators of Cell Cycle
In normal tissue, the rate of cell division is balanced by the rate of cell loss or destruction. Mitotic rates are genetically controlled and many different stimuli may be responsible for activating genes that promote / inhibit cell division.
Proto-oncogenes. They are found in normal human cell carrying codes for cell surface receptors, growth stimulatory proteins and other proteins that control cell division. When activated, they stimulate cell division in a normal cell. To halt cell division, these genes must be inactivated.
Tumor suppressor genes. They inhibit cell division in a normal cell to prevent inappropriate growth. These genes must be inactivated or gene products must be absent for cell division to occur. The gene p53 codes for protein p53 that resides in the nucleus and activates genes that direct the production of growth-inhibiting factors inside the cell. This protein halts cell division and induces abnormal cells to undergo apoptosis, a major backup system to prevent cancerous growth. Roughly half of all cancers are associated with abnormal forms of the p53 gene.
Contact Inhibition / Density-Dependent Inhibition. A population of cells competes for nutrients and minute quantities of growth regulators. Apparently, when cells reach a certain density, the amout of these required substances per cell is insufficient to allow continued growth of the cell population. To divide, most cells require adhesion to substratum (i.e. the extra-cellular matrix of a tissue). Cells normally stop dividing if they lose their anchorage. Density-dependant inhibition probably functions in the body’s tissues, checking the proliferation of cells at some optimal population density. Cancer cells do not exhibit this mechanism.
Platelet-Derived Growth Factor (PDGF). Platelets release a chemical called PDGF when they cone into contact with a damaged blood vessel wall. Fibroblasts, the main cells of connective tissue, have receptors for PDGF on their plasma membranes. The binding of PDGF stimulates the fibroblasts in the area of the wound to divide rapidly, causing the wound to heal.
Environmental factors. Changes in temperature and pH and declining nutrient levels lead to declining cell division rates.
15. Why does Cancer Develop
Although the ultimate cause or causes of the many existing forms of cancer are still unknown, there are specific factors that are often associated with the disease that they are considered either to increase a person’s risk to cancer or create a likely setting for cancer to develop.
Exposure to mutagens. Most researchers believe that most cancers develop only after repeated contact with carcinogens and radiation, the substances that cause or promote the development of cancer. They usually cause mutation / damage to DNA that contains the genes that control normal rate of cell division.
Over-expression of Proto-oncogenes. These genes, which stimulate cell division in normal cells, mutate to become more active (then called oncogenes) but the expression of tumor suppressor genes remains normal.
Under-expression of Tumor Suppressor genes. These genes, which normally inhibit cell division, become less active but the expression of proto-oncogenes remains normal.
16. Characteristics of Cancer Cells
They undergo uncontrollable, rapid cell division such that rate of cell division exceeds the rate of cell death. They are unable to carry out normal cell functions. They are able to infiltrate surrounding tissues and able to metastasise.
17. How does Cancer Develop
When the rate of cell division exceeds the rate of cell death, a tissue enlarges. A tumor, or neoplasm, is an undifferentiated mass or swelling produced by abnormal cell growth and division. In a benign tumor, the cells usually remain within a connective tissue capsule. Such a tumor seldom threatens am individual’s life. The tumor can be surgically removed if its size or position disturbs tissue function.
Cells in a malignant tumor no longer respond to normal control mechanisms. These cells spread into surrounding tissues from the primary tumor. This process is called invasion. Cancer cells may also travel to distant tissues and organs and establish secondary tumors. This dispersion is called metastasis, which is dangerous and difficult to control.
Cancer disease is characterized by malignant cells which undergo a series of rapid cell divisions before they reach “functional maturity”. Cancer develops in the series of steps. Initially, the cancer cells are restricted to the primary tumor. In most disease, all the cells in the tumor are the daughter cells of a single malignant cell.
Cancer cells generally lose their resemblance to normal cells. They change size and shape, typically becoming abnormally large or small. At first, the growth of the primary tumor distorts the tissue, but the basic tissue organization remains intact. Metastasis begins with invasion as tumor cells “break out” of the primary tumor and invade the surrounding tissue. They may then enter the lymphatic system and accumulate in nearby lymph nodes. When metastasis involves the penetration of blood vessels, the cancer cells circulate throughout the body.
Responding to cues, cancer cells within the circulatory system ultimately escape out of the blood vessels to establish secondary tumors to other sites. These tumors are extremely active metabolically, and their presence stimulates the growth of blood vessels into the area. The increased circulatory supply provides additional nutrients and further accelerates tumor growth and metastasis.
Organ function begins to deteriorate as the number of cancer cells increases. The cancer cells may not perform their original functions at all, or they perform normal functions in an unusual way. Endocrine cancer cells may produce normal hormones but in excessively large amounts. Cancer cells do not use energy very efficiently. They grow and multiply at the expense of healthy tissues, competing for space and nutrients with normal cells. This competition accounts for the starved appearance of many patients in the late stages of cancer. Death may occur as a result of the compression of vital organs when non-functional cancer cells have killed or replaced the healthy cells in those organs or when the cancer cells have starved normal tissues of essential nutrients.
The growth of blood vessels into a tumor is a vital gap in the development and spread of cancer. Without those vessels, the growth and metastasis of the cancer cells will be limited by the availability of oxygen and nutrients. A peptide called anti-angiogenesis factor can prevent the growth of blood vessels and can slow the growth of the cancer. This peptide, produced in normal human cartilage can be extracted in huge quantities from sharks, whose skeletons are entirely cartilaginous.
18. Main Types of Cancer
Carcinoma represents 90% of all cancers. They arise from epithelial cells that cover external and internal body surfaces.
Sarcoma represents 5% of all cancers. They arise from supporting tissues of mesodermal origin.
Lymphoma and Leukaemia represents the last 5% of all cancers. They arise from cells of blood and lymphatic origin. Leukaemia occurs when cancer cells circulate in large numbers in the blood stream rather than growing mainly as solid masses of tissue.
19. Cancer Risk Factors and Precautionary Actions
19.1 Lifestyle and Diet
19.1.1 Smoking
Smoking causes 30% of all cancer deaths. This makes tobacco smoke the single most lethal carcinogen. Smoking causes cancer of the lung, upper respiratory tract, oesophagus, bladder and pancreas and may also cause cancer of the stomach, liver, kidney, colon and rectum.
Second-hand smoke also causes a few thousand deaths from lung cancer among non-smokers. Lung cancer survival rate is low because lung cancer usually goes undetected until it is too late and has spread. The single most effective way to reduce lung cancer risk is to quit smoking and limit exposure to second hand smoke.
19.1.2 Alcoholism
Alcohol is estimated to contribute to about 3% of deaths from cancer. People who drink alcohol heavily have a higher risk of mouth, throat, oesophagus, stomach and liver cancer. Although alcohol appears to reduce the risk of heart disease, evidence also suggests that even one alcoholic drink a day is associated with breast, colon and rectal cancer.
19.1.3 Carcinogenic Foods
Salted, pickled and smoked foods such as smoked fish and meats treated with nitrites should be limited. Salt appears to contribute significantly to cancer. Meats that have been charred or over grilled should be eliminated from the diet because the charred part is carcinogenic. Taking the antioxidant vitamin C through vitamin C rich foods or supplementation may protect against the cancer causing effects of carcinogenic foods.
19.1.4 Free Radicals
They are dangerous, highly reactive chemical compounds that can damage DNA and lead to cancer. They are generated in various ways.
Polyunsaturated fats tend to oxidize and thus form free radicals. A build up of free radicals in a person’s system occurs when the body’s own biochemical mechanisms for reducing their levels cannot keep up with their production and there becomes an abundance of free radicals in the system.
In this case, it is important that the body be supplemented with antioxidants to finish up the job. Antioxidants block oxidation and thus free radical formation. Vitamins C and A are excellent antioxidants and can be taken through supplementation as well as a diet high in yellow and orange fruits and vegetables.
19.1.5 Unhealthy Diet
Animal fat, and especially that from red meat, is associated with several different types of cancer including the colon, rectum and prostate. The effect of diet on cancer may have much to do with the foods that are in the diet as foods that are not in the diet.
Adopting certain dietary habits, such as reducing dietary fat and eating more soy-based foods, fibres, fruits and vegetables, can offer some protection against cancer because they contain certain properties such as antioxidant activity that can act as cancer blockers.
19.2 Genetic Predisposition
Certain types of cancer often run in families. It is the predisposition to cancer that is inherited. Other non-genetic factors must be present for cancer to develop. These factors can either promote or hinder cancer, thus allowing or not allowing the disease to develop. If there is cancer in your family, it does not necessarily mean that you wi get cancer because environmental factors play a role also. However having a family history of cancer does mean that you are at a higher risk.
19.3 Over-exposure to Oestrogens
19.3.1 Menarche, Menopause and Pregnancy
If a woman’s system is exposed to too much oestrogen in her blood system, it puts her at an increased risk for some gynecological cancers. This is because oestrogen stimulates cell proliferation in these tissues. A woman’s exposure to oestrogen is determined by a variety of factors, such as age at menarche, pregnancy and age at pregnancy, age at menopause, weight, physical activity and diet.
A woman with an early age at menarche and late age at menopause would have had a higher exposure to oestrogen than a woman with a later age at menarche and earlier menopause, assuming dietary and other factors are constant. To lower the risk, you could have a baby before 35 years of age.
19.3.2 Hormone Replacement Therapy (HRT)
There appears to be an association between increased risk and the use of HRT in post-menopausal woman. There are some new “designer” oestrogens which may be helpful to a woman’s bones and cardiovascular system just like oestrogens are, but which do not have the potential negative effect on the breast or uterus.
19.3.3 Environmental Oestrogens
Certain chlorinated compounds e.g. polychlorinated biphenyls (PCBs), pesticides and industrial pollutants in the environment have weak oestrogenic effects. Like oestrogen, they encourage proliferation of breast cells.
19.4 Radiation Exposure
19.4.1 Ionizing Radiation
Potential sources of ionizing radiation include nuclear explosion and medical diagnostic and therapeutic procedures. Overexposure to ionizing radiation can cause DNA mutation that may lead to cancer.
Your risk of DNA damage from ionizing radiation depends on how much of this type of radiation you have received over your lifetime. So it is a good idea to reduce the number of X-rays you receive by only getting them only when necessary.
Other ways to reduce your exposure to ionizing radiation are not living near a nuclear power plant or nuclear waste disposal site and making sure your home does not have dangerous levels of radon, a radioactive gas emitted from the earth in some geographic regions.
19.4.2 Ultraviolet Radiation
UV radiation is the radiation from the sun that reaches the earth. The most harmful of this type of radiation are the high frequency, DNA-damaging UV-B rays that cause 90% of skin cancers. Cover up with clothing and sunscreen with high SPF. Be especially sure to cover up those areas that are most susceptible to skin cancers.
19.5 Carcinogenic Chemicals
Chemical carcinogens such as asbestos, benzene, formaldehyde and diesel exhaust are dangerous in high concentrations. This level of concentration often used to exist in some workplaces. Strict control over the past 50 years of such occupational carcinogens has greatly reduced cancers caused by these substances.
19.6 Viral Infection
Some viruses carry
oncogenes which may be introduced into then cells. Oncogenes are
proto-oncogenes that have mutated to become more active in stimulating cell
division. They cause affected cells to divide uncontrollably. In human,
infection with some forms of the papilloma virus can lead to cervical cancer
while hepatitis B virus may cause liver cancer to develop.
