D2.1.8-2.1.17 Cell Biology PDF

Continuity and change D2.1.8 Identification of phases of mitosis Preparing and viewing a stained slide: Preparing a root tip squash 1. Suspend the base of a clove of garlic in water using 3. Cut off about 20 mm to 30 mm from the end of two toothpicks fo...

Continuity and change D2.1.8 Identification of phases of mitosis Preparing and viewing a stained slide: Preparing a root tip squash 1. Suspend the base of a clove of garlic in water using 3. Cut off about 20 mm to 30 mm from the end of two toothpicks for 3 days or more, until roots grow. Cut off or three of the roots and immerse these root tips roots and fix them in 99 parts of 70% ethanol to part in 1% toluidine blue stain. Skin protection needed! of pure ethanoic acid for 24 hours. The stain binds to DNA making chromosomes more visible, 2. When you are ready to make observations, immerse the roots in 0.1 mol dma hydrochloric acid at 400C for 4. Rinse the stain off the root tips and gently squash five minutes. Eye protection needed! Then rinse off them under a cover slip. Observe the slide using the the acid. This acid treatment loosens the cell walls in low power objective followed by the medium power the root tissue. objective. Data-based questions: Identifying phases of mitosis a. There are five cells in the right-hand column, Zi to Zv. Identify which of these cells are in interphase. b. Identify the phase for each cell in column Z thatis dividing its nucleus by mitosis. 2. Identify the phase for each of cells Vi, Vii, Wi, Wii, Wiii, Xiii. 3. There are five whole cells in column Y (Yi to W). Identify which, if any, of these cells is in: a. prophase b. metaphase. 4. Identify two cells in which cytokinesis has begun. 5. Cell Yi (the uppermost whole cell in column Y) hasa different appearance from others in the micrograph. Suggest what proness caused this cell to have height in the column smaller its width. Figure 17 This micrograph shows cells in the tip of an onion 6. Cell Wi has two in its nucleus. They are root, magnified x600. sites where ribe.scre: being assembled. Suggest reasons why ceo reeds more ribosomes. Some of the cells are in mitosis and others are in Identify,with a win:ch cell in the micrograph interphase. The columns of cells are indicated by letters 7. (V to Z) and the cells within the columns by numbering probably entered Ente;ohase most recently. from the top (it ii, etc.). 620  Cells 02.1.9 Meiosis as a reduction division of a cell contains the chromosomes. Each chromosome Thenucleus is a very with some associated proteins. longDNA molecule Along a chromosome is genes. An average human chromosome asequenceof has about a thousand in a linear sequence. When the DNA in a genes chromosome is replicated, the does not change. This means the sequence genesequence of genes shows the generations in a species, continuitythrough potentially over millions of years. Thereare majordisadvantages to changes in gene sequence, and such changes during the evolution of new species. areonlycommon Chromosomes with the of genes as each other are homologous. samesequence Althoughthe sequence of genes on a chromosome is resistant to change, the basesequence of individual genes on a chromosome can change by mutation, resultingin new alleles. These alleles can be reshuffledduring meiosis to produce newcombinations. This is called recombination and together with gene mutation itexplainshow chromosomes can be homologous but not identical. A species has a characteristic number of types of homologous chromosome. This is knownas the haploid number and is given the symbol n. Body cells in most plantsand animals contain two homologous chromosomes of each type, so there are2n chromosomes. This is the diploid number. The terms haploid and diploid areimportantin cell biology and genetics. Haploid (n)—a nucleus, cell or organism with a single set of chromosomes, which are all non-homologous Diploid (2n)—a nucleus, cell or organism with two sets of chromosomes and therefore homologous pairs of chromosomes. Diploidcells are produced by sexual reproduction. The key event is the fusion ofgametes; for example, a sperm and an egg uniting to form a single cell. Gametesare haploid, so the zygote produced when male and female gametes fuseis diploid. Body cells in most plants and animals are produced from the zygote by many cycles of mitosis and cell division, so are all diploid. This continuityin the genome and chromosome number of an individual persists untilsexual reproduction. If diploid body cells were to become gametes, the resultingoffspring would be tetrapioid (4m).Tetraploid gametes would result inoctoploid offspring. To prevep.tthe number of chromosomes doubling with each generation in a species, gametes must be haploid. In a sexual life cycle, theremust therefore be a reduction division in which the chromosome number is halvedfrom diploid to haploid. This counteracts the doubling effect of the male andfemale gametes fusing. Meiosis is this reduction division (Figure 18). Inmostorganisms, normal body cells are all dipioid; meiosis happens during the process of gametogenesis. There are some other patterns. For example, mossescarry out meiosis earlier in the life cycle and the main moss plant is haploid. Meiosis must occur at some stage in a sexual life cycle to avoid increases in the chromosome number. Figure 18 diagrammatically compares mitosisand meiosis. 621  Continuityand change Mitosis Meiosis prophase homologous homologous chromosomes remain chromosomes pair unpaired as they up and condense condense in these pairs microtubules from the microtubules from the two poles link to two poles link to different different sister chromatids homologous chromosomes in each chromosome in each pair anaphase sister chromatids homologous chromosomes separate from each separate from each other other and move to and are pulled to opposite opposite poles poles telophase two diploid nuclei two haploid nucleiare are formed and the formed and both of chromosomes inside them prepare the second them decondense division of meiosis second division of meiosis phases in the second Figure 18 Mitosis is a single division producing division of meiosis are two diploid daughter cells. Meiosis is a double division similar to mitosis, with producing first two daughter cells, each with a haploid chromatids separating, nucleus. These two cells divide again to produce a total of producing a total of four four cells, each with a haploid nucleus. There are therefore haploid nuclei two rounds of chromosome segregation during meiosis ATL Communication skills: Responding appropriately to command terms The command term "compare and contrast" requires that students consider the similaritiesand differences of a particular phenomenon in a variety of contexts. Two separate descriptions do not meet the requirementsof this command term. features features features For example, if asked to compare and contrast the unique common unique behaviour of homologous chromosomes in mitosis to to to and meiosis, a student should write in this style: "In meiosis both mitosis meiosis l, homologous pairs form a bivalent and line up along the equator, whereas in mitosis, the homologous chromosomes behave independently when they line up along the equator." In this case, the comparative term A Figure 19 One strategy is to use a Venn diagram "whereas" is essential. Furthermore, responding to this like this to show similarities and differences. command term encourages the inclusion of at least one similarity and at least one difference. 622  Cells Data-basedquestions: Life cycles life cycles of humans and mosses; n figure20 The representsthe haploid sporophytes of mosses grow on the main moss plant numberof chromosomes number. and consist of a and 2n represents the diploid stalk and a capsule in which spores are produced egg n sperm egg sperm n n moss Key male zygote human female human plant mitosis 2n n zygote 2n 2n fertilization spore sporophyte n 2n Figure 21 Cells in the green cushion of this moss are haploid. l. Compare the life cycle of a moss The stalks and spore capsules and of a human by giving five growing out from it are diploid similarities. sporophytes, so genetically they are each new individuals. The 2. Distinguish between the life cycles moss of a moss and a human by giving is Leptostomuminclinans, growing on a tree in Waimarama Sanctuary five differences. [51 near Nelson in New Zealand D2.1.10 Down syndrome and non-disjunction Ifthechromosomes eparate correctly, four haploidcells are pr.-ed by meiosis in a non-disjunction in non-disjunction in diploidcell. Anaphase I Anaphase Il Homologous. csomes separatefrom eachother and to opposite poles in Anaphasel, hamangthe chromosome number Chromatids in each chromosome separate fromeach other and move to opposite poles in Anaphase ll. Errors mayoccur. For example, a pair of homologouschromosomes might move to the samepole in Anaphase l, or both chromatids of Onechromosome might move to the same pole in Anaphasell. This is called non-disjunction and the COnsequence is cells with one chromosome extra ormissing. A Figure 22 Failure of chromosomes to separate is called non-disjunction 623  Continuity and change Non-disjunction can happen with any diploid cell with the of chromosomes. In almost all cases, a normal two copies of missing chromosome 21 chromosome quickly leads to the death of a haploid cell, because genes coding for non-disjunction essential polypeptides are lacking. Havingan during meiosis extra chromosome is also a lethal normal haploid haploid cell lacking condition in most cases. It might lead to the death gamete chromosome 21 ofa haploid cell produced by meiosis or the cell dies of the zygote or embryo produced by death fusion of gametes. zygote with three normal haploid In a few cases an extra chromosome is not copies of chromosome 21 gamete lethal. For example, Down syndrome is due instead of the usual two to a non-disjunction event that results in a person A Figure 23 How non-disjunction can lead to Down syndrome. having three copies of chromosome number 21 Chromosomes 1 to 20, 22, X and Y are not shown While individuals vary, some of the featuresof the syndrome are hearing loss, heartand vision disorders. Non-disjunction can also result in the birth of babies with abnormal numbers of sex chromosomes. Klinefelter's syndrome is caused by having the sex chromosomes XXY Turner's syndrome is caused by having only one sex chromosome, an X. A Figure 24 Child with Down syndrome C Data-based questions: Parental age and non-disjunction Studies show that the age of parents influences the 4. Discuss the risks and benefits of parents not chances of non-disjunction. Data in Figure 25 shows the having children until they are relatively old. relationship between maternalage and the incidence trisomy 21 of Down syndrome and other conditions caused by a}!chromosomal chromosome abnormalities. abnormalities 14 1. Outline the relationship between maternalage and the incidence of chromosomal abnormalities 12 in live births. 10 2. a. For 40-year-old mothers, determine the probability that their baby will have Down 8 syndrome. 6 b. Using the data in Figure 25, calculate the 4 probability that a mother aged 40 will give birth to a child with a chromosomal 2 abnormality other than Down syndrome. 3. Only a small number of possible chromosomal 20 40 60 abnormalities are ever found among live births. maternal age / years More than half of all cases are Down syndrome. A Figure 25 The incidence of Down syndromeand other Suggest reasons for these trends. chromosomal abnormalities as a function of maternalage 624  cells D2.1.11 Meiosis asa source of variation genetic diversity in two ways: generates random orientationof Meiosis bivalents chromosomes that have paired up) and mologous crossing over.At the startof pairs ofhomologous chromosomes, one (ho thereare originally inherited from the meiosis havethe some of the genes will be different. allelesof Crossingover HomologOUSchromosomes pair up at an early stage of meiosis. Because DNA already occurred, each chromosome replicationhas consists of two chromatids, four DNA molecules associated in each sothereare pair of homologous chromo- somes. A pair of homologous chromosomes is called a bivalent and the pairing synapsis. processis called crossing over takes place while the chromatids are still very elongated. Two non-sisterchromatids are brought together at the same point along their gene sequences. The two strands of their DNA double helices are cut, one at a time, andare rejoined with the equivalent strand in the other chromatid. This results in a mutualexchange of DNA and therefore genes between the two chromatids. homologous chromosomes with sister chromatids formed chiasma formed by thesame sequence of genes but by replication and then held crossing over between differentalleles of some genes together by cohesin loops non-sisterchromatids one kinetochore formed on each homologous chromosome which will move remove it to a pole Gl of G2 of first ±nterphase interphase metaphase of meiosis A Figure 26 Chiasma formation as a consequence of crossing over ABCDEF*VWXYZ ABCDEF*VWXYZ ABCDEF*VWXYZ ABCDEF*VWxyz crossing over abcdef*vwXYZ abcäef*vwxyz abcdef*vwxyz abcdef*vwxyz A Figure 27 Recombination of alleles by crossing over As non-sisterchromatids are homologous but not identical, some alleles of the exchanged genes are likely to be different. Chromatids with new combinations Ofalleles are therefore produced. The consequences of a crossing over can be illustratedusing upper- and lowercase lettersfor alleles of genes. Crossing over occurs at random positions anywhere along the chromosomes. At leastone crossover occurs in each bivalent, but there is often more than one. 625  Continuity and change Random orientation of bivalents Each homologous pair of chromosomes forms a bivalent on the equator of the cell during first metaphase of meiosis. Within each bivalent, the homologous chromosomes become attached to spindle microtubules from differentpoles. Which chromosome of a pair attaches to which pole is decided by chance because orientation of bivalents at this stage is random. There is a 50% chance of each of the two possible outcomes. Although random, the orientationof bivalents has consequences, because the two homologous chromosomeshave different alleles of some genes. Whether one particular allele is inherited by an individual depends only on which way a bivalent happened to be facing when spindle microtubules were attached. Figure 28 Five chiasmata are visible in this bivalent, showing that crossing over can occur more than once The position of one bivalent does not affect other bivalents—theirorientation is independent. The number of possible combinations of chromosomes that a haploid cell produced by meiosis could contain as a consequence of the random orientation of bivalents is therefore 2n where n is the numberof bivalents (and also the haploid number for the species). With two pairs of bivalents, as in the diagrams, there are four possible combinations, but most species have more chromosomes than this, so more possible outcomes. In one human individual, random orientation of bivalents in meiosis can generate 223possible outcomes—more than 8 million. Combined with crossing over this gives almost limitless numbers of possib\e combinations of alleles in cells produced by meiosis, either or Mitosis Meiosis A Figure 29 Comparison of chromosomeattachmentto spindle microtubules 626  cells division of meiosis first I prophase Homologous chromosomes form parallel (synapsis) pairs nuclear membrane occurs between non-sister Crossingover chromatidsin each bivalent spindle microtubules and centriole Chromatids (four per bivalent) shorten (condensation) and thicken Prophase I Metaphase I Nuclear membrane disperses and homologous chromosomes in each bivalentbecome attached to spindle microtubulesfrom opposite poles bivalents aligned on the equator Bivalents spread out in the equator pairingof homologous chromosome Metaphase I ends but chiasmata prevent separation Anaphase I Kinetochores shorten the spindle microtubules, pulling chromosomes homologous towardsthe poles chromosomes being pulled to Chiasmata slide to the end of opposite poles chromosomes Pairsof homologous chromosomes Anaphase I separateand move to opposite poles Telophase I A nuclear membrane is assembled around the chromosomes at each pole of the cell cell has divided Chromosomes decondense, but in some across the equator species only partially Cytokinesis d;vides the cytoplasm, Telophase I resultingin haploid cells 627  Continuityand change The second division of meiosis Prophase Il DNA replicationdoes not occur between the firstand second divisions because the chromosomes each have two chromatids already. Because of this, and because there has been crossing over, the two chromatids in each chromosome are not genetically identical, unlike mitosis Prophase Il Chromatids are condensed Metaphase Il Nuclear membranes disperse and the chromatids of each chromosome become attached to spindle microtubules from opposite poles Chromosomes spread out on the equator Cohesin loops connecting chromatids are cut allowing them to start to separate from Metaphase Il each other Anaphase Il Kinetochores on the centromere of each chromatid shorten the spindle microtubules, pulling the chromatids to opposite poles The chromatids are considered to be chromosomes once they have separated By the end of anaphase these chromosomes Anaphase Il have reached the poles Telophase Il Nuclear membranes are assembled around the chromosomes at each pole Decondensation spreads the chromosomes out throughout each of the four nuclei Cytokinesis occurs, dividing both of the cells produced by the first division of meiosis, so Telophase there are now four haploid cells D2.1.12 Cell proliferation for growth, cell replacement and tissue repair Cell proliferation is a rapid increase in the number of cells. It happens when cell division happens at a faster rate than cell death. Cell proliferation is needed in multicellularorganisms for growth, cell replacement and tissue repair.Mitosis ensures continuity of the genome during cell proliferation in an animal, plantor other multicellular eukaryote. 628  Cells Growth there are embryonic and juvenile dome of cells at centre mostanimals, phases of growth, of apical meristem is reached and growth stops. after which dultsize and form Initially,there is cell animal embryo. In some parts of proliferation ff@uglnoutan the body, cells during juvenile phases of growths continue to proliferate For example, are active in childhood growth plates near youngest bones and theend of adolescence, with cell bone growth and rapid increase in divisions developing contributingto height. leaf in plants is confined to cell proliferation growth regions called developing region of are found at the tips of stems meristems. Apical meristems and roots. Some of bud stem growth the daughtercells formed by division remain in an apical meristem at and continue to divide.Cells formed the margin of the meristemcease divisions and instead enlargeand differentiate for a specific function. The root apical meristem A Figure 30 Structureof a shoot apical generatescells for lengthening the root. The shoot apical meristem meristemthat is producing cells for stem is more complex,producing cells for extension growth of the stem and growth and leaf development for developing leavesor flowers. Cellreplacement Ifcellsare lost from a tissue, more cells must be producedto replace them. This happens in the epidermisof the skin, where cells are abraded and replacedthroughout life. Cell division happens in the basallayer of the epidermis. Cells produced here are displacedtowards the skin surface by continued cell division.During this transit, cells produce large amounts ofthe tough protein keratin, which is hydrophobic and causesthe cells to dry out. By the time the cells reach the A Figure 31 Cell proliferationin a sea urchin begins with a large skinsurfacethey are flattened and dead. Frictioncauses zygote, which divides repeatedly, passing through the four-cell stage themto be rubbed off after they have waterproofed and (left)and the blastula(right)which is a hollow ball of cells. All the cells protectedthe body for a while. in the blastulacontinue to divide through the following embryonic stages it is debatable whether cell replacement is a true exampleof cell pro;iferation because cell division does not happen at a faster rate than cell death, but cell proliferation !la:nens in one part of the epidermis cells in this region stop dividing and then and cell death in;a-other. grow larger and differentiate so they can perform a specific role in the root Tissuerepair Woundsto marr; rwts of the body can heal, using cell division to !zce lost cells. This depends on the presence of undifferentiated stem cells that can cell proliferationin this region produces divide and then differentiate. Numbers of these stem the cells needed for the root to grow in cellsvary, so some tissues are more able to repair length. The cells remain small because themselves than others. they divide as soon as they are large enough Skin is particularly effective at undertaking tissue repairafter a cut or other wound. If the basal cells in theepidermis are still present, they can regenerate cell proliferationin the root cap replaces damaged outer layers of skin in a few days. Stem cells cells that are rubbed off as extension inthe dermis can repair deeper damage, though this growth pushes the root through the soil takeslonger. If damage is so severe that there are no survivingstem cells, skin grafts may be needed. A Figure 32 Longitudinal section through an onion root apical meristem 629 Continuity and change D2.1.13 Phases of the cell cycle Cell proliferation is achieved by cells following the cell cycle. There are two main phases in this repeating sequence of processes. Mitosis is the process that divides the nucleus, after which cytokinesis divides the cell as a whole. Mitosis is subdivided into four stages: prophase metaphase, anaphase and telophase (Section D2.7.7). Interphase is the period between one mitosis and the next. In interphase DNA is replicated, mitochondria divide and other cell components are synthesized. Interphaseis subdivided into three stages: Gl (Gap 1),S phase and (32(Gap 2). e—the phase after mitosis and before DNA replication when each chromosome is a single DNA molecule. This is an active growth phase. division S phase—in which all DNA in the nucleus is replicated. This results in identical pairs of DNA molecules held together by cohesin loops. The loops remain MITOSIS until the end of metaphase in mitosis, ensuring that the two molecules can be dispatched to different daughter cells. INTERPHASE G2—the phase after all DNA in the nucleus has been replicated so each s chromosome consists of two DNA molecules or chromatids. Growth may resume during this phase while the cell is preparing for mitosis. Instead of moving on to mitosis or Gl again, cells produced by mitosis and A Figure 33 Sequence of phases in the cytokinesis may leave the cell cycle and enter Go (Gap zero). In Go, cells grow and cell cycle differentiate for a specific role, but do not divide again. Of the two cells produced by one turn of the cell cycle, one or both may leave the cycle and enter Go. C Data-based questions: DNA content per nucleus The amount of DNA present in each cell nucleus was a. bone marrow cells in prophase of mitosis measured in many cells taken from two different cultures b. bone marrovv in telophase of mitosis. of human bone marrow (Figure 34). 3. Explain how many chromosomes there are likely to 1. For each group (l, Il and Ill) in Sample B, deduce be in cells in: which stage of the cell cycle (S, Gl or G) the cells a. Sample A could be in. b. Groups I and 'r, Sample B. 2. Estimate the approximate amount of DNA per 4. Explain the mass of DNA that human egg and nucleus in these human cell types: sperm cells are likeiy to contain. Sample A Sample B 3 (non-dividing cell culture) (rapidly dividing cell culture) 3 o c 2 c 2 o o Il 5 10 15 5 10 15 Figure 34 Graphs of DNA per nucleus DNA/pg per nucleus DNA/ pg per nucleus 630  D2.1.14 Cell growth during interphase the state of a cell when not Interphaseis undergoing or meiosis. DNA in regions lacking mitosis genes ed for the cell's activities, remains condensed heterochromatin.The rest of the DNA as becomes decondensedand dispersed in the nucleus as state can be chromatin. DNAin a decondensed transcribed, allowing synthesis by translation of mRNA. protein the cell cycle typically cellsfollowing need to double in sizeduring interphase. DNA is doubled by replication. The volumeofcytoplasm increases, so molecules within it such s enzymesmust be synthesized. The area of membrane withincells is increased, requiring extra phospholipids, membraneproteins and cholesterol. Thenumbersof most types of organelle must be increased. Mitochondriaand chloroplasts contain DNA, so can only bepropagated by division, following DNA replication and organellegrowth. Other membrane-bound organelles such asGolgi bodies bud off from existing ones. Non-membrane- boundorganelles are assembled de novo. Ribosomes,for example,are assembled in a region of the nucleus called the nucleolus. Interphaseis an active phase in the life of most cells, with manymetabolic reactions occurring. Some of these, such asthereactions of cell respiration, also occur during mitosis andmeiosis, but the biosynthesis of protein and other moleculesneeded for growth is a hallmark of interphase. A Figure 35 Electron micrograph ofa cell in interphase from the intestinewall, with false colour showing the nucleus (dark blue), Golgi bodies (pink) and mitochondria (purple). There are regions of heterochromatin near the margins of the nucleus D2.1.15 Control of the cell cycle usingcyclins Thecell cycle read' a coordinated sequence of changes to happen in a cell.There are chet ;nints in the cycle to hold cells until it is appropriate forthemto t') the next phase. These checkpoints are also used to ensurethat cells dividing when there has been enough cell proliferation in a tissue. A group of proteins called cyclins coordinates the sequence of changes during thecell cycle. Cyclins activate enzymes called cyclin-dependentkinases,which bindphosphate to other proteins, activating them. In this way, each type of cyclin activatesa group of proteins that carry out the actions required during a specific Phaseof the cycle. This ensures that all actions are performed at the correct time andthatthe cell only moves past checkpoints in the cycle when it benefits the wholeorganism. Thereare four main types of cyclin in human cells. Figure 36 shows how the levels Ofthemrise and fall. Unless these cyclins reach a threshold concentration, a cell doesnot progress to the next stage of the cell cycle. 631  Continuity and change Gl phase S phase G2 phase mitosis Cyclin D triggers cells to move from Go to (31and from Gl into S phase. Cyclin E prepares the cell for DNA replication in S phase. Cyclin A activates DNA replication inside the nucleus in S phase. Cyclin B promotes the assembly of the mitotic spindle and othertasks Figure 36 Cyclins and the cell in the cytoplasm to prepare for mitosis. D2.1.16 Consequences of mutations in genes that control the cell cycle Control of the cell cycle ensures that tissues have enough cells, but not too many. Sometimes control is lost in an individual cell because of mutationsto its genes. When this cell divides, its daughter cells inherit the loss of control, so also divide. The result is a group of cells that increases in number exponentially withoutthe normal controls. This is how a tumour originates. Mutagens increase the chance of tumour formation. There are two mainclasses of mutagen that do this. Mutagenic chemicals—the InternationalAgency for Research on Cancer lists over 50 substances or groups of substances that are "definitelycarcinogenic", All forms of high-energy radiation such as X-rays and ultraviolet, but not visible light or other forms of low-energy radiation. There are two groups of genes that can c.hange a normal cell into a tumour cell if they mutate. Proto-oncogenes have a variety of co!es in the ceil. Some regulate expression of genes concerned with cell prohieratiüiT Others have roles in secondary messenger systems that control the cel; cycle. A third group is concerned with growth factors or receptors for them. Proto-oncogenes can mutate into oncogenes, which actively promotecell proliferation and are genetically dominant. So, only one of a pair of proto- oncogenes in a diploid cell has to mutate for an oncogene to be formed, increasing the chance of a tumour. Usually, a mis-sense mutation changes one of the amino acids in the polypeptide coded for by the gene, makingit A Figure 37 The tumouron this patient's super-active. forehead was large but benign and was removed easily without any further Tumour-suppressor genes prevent cell proliferation. Some of them function treatment being needed as brakes at checkpoints in the cell cycle. Others are needed for DNA repairto 632  Cells errors in replication and thus reduce programmed cell death (apoptosis) mutation rates. A third rolesin within cells group has DNA damage. where there irreparable has been Mutationsto tumour-suppressor genes increase gene product no longer functions the risk of tumour formation triplet properly. Base change a of bases coding for substitutionmutations an amino to cause loss of function, acid into a stop codon arevery likely because they oftruncated polypeptides. However, such result in production of mutationsare ifone of a pair tumour-suppressor genes in recessive because a cell is polypeptides are produced unmutated, some and the risk of increased. tumour formation is not Anycell in the body can become a tumour cell, but mutation usuallyenough. As many as 10 mutations must to one gene is not be present together cellfor some types of tumour to be formed. The in a single chance of all these happening in a single cell is extremely small. mutations However, there are Ofcellsin the body and humans have long vast numbers lifetimes, with mutation anytime. The chance of tumour formation is also possible at increased by a mechanism A Figure 38 This large growth on the hasparallels with evolution by natural selection. that Mutated genes are passed trunk of a beech tree is a plant tumour, daughtercells when a cell divides and each to mutationthat increases the caused by the pathogen Agrobacterium celldivision will result in a larger pool of cells in rate of which furthermutations tumefaciens.Although plants sometimes needed fortumourformation could occur. develop tumours, they do not develop cancer. What hypothesis could account for Mostpeople will therefore develop tumours during their life, but the this? majorityare harmless or treatable. In all cases, the variables that affect outcomesmost are tumour type, promptness of detection and effectiveness of medical treatment. D2.1.17 Differences between tumours in rates of cell division and growth and in the capacity for metastasis and invasion of neighbour;og tissue Whena tumour cefi has been formed it divides repeatedly to form two, then four, theneight cells and on. This group of cells is the primary tumour.Often the cells in a primary turnour adhere to each other so they remain as a single mass. Suchtumours are to cause much harm and are classified as benign. They shouldnot be thought of as cancer. Inothercases, cell-to-cell adhesion is not adequate to prevent cells becoming detachedfrom the tumour. The cells may invade neighbouring tissues or, if a transportroute such as blood or lymph is available, they may move elsewhere inthe body. The spread of tumour cells from one part of the body to another is knownas metastasis. If conditions are suitable, the cells that have metastasized continuedividing and develop into secondary tumours. Usually,multiple secondarytumours develop, so the consequences are greater than with a single primarytumour. Tumours that spread in this way are classified as malignant and causewhat is commonly known as cancer. Certain tissues are more likely to Produce malignant tumours, especially in breasts, ovaries, testes and the thyroid glandwhere there is hormonal stimulation of cell division. 633  Continuity and change A diagnosis of cancer is always worrying for a patient, but effective treatments have been developed for many types of tumour. Also, the rate of cell divisionand growth in tumours is variable and in some cases is very slow. A Figure 39 MRI scans are used to check for the spread of cancer. The left scan shows normal brain tissue (purple). The right scan shows multiple secondary tumours due to metastasis of a primary tumour in the breast Interpretation of a micrograph: Determination of a mitotic index The mitotic index is the ratio of the number of cells in mitosis in a tissue to the total number of observed cells. It can be calculated using this equation: number of cells in mitosis mitotic index = total number of cells Figure 40 is a micrograph of cells from a tumour in breast tissue. The mitotic index for this tumour can be calculated if the total number of cells in the micrograph is counted and the number of cells involved in cell division in the same area is counted. To find the mitotic index of the part of a root tip where cells are proliferating rapidly, follow these instructions. Obtain a prepared slide of an onion or garlic root tip. Find and examine the meristematic region (that is, a region of rapid cell division). A Figure 40 Cells in a breast tissue tumour.What is the mitotic Create a tally chart. Classify each of about a hundred index for this tumour? cells in this region as being either in interphase or in any of the stages of mitosis. Use this data to calculate the mitotic index. 634  Data-based questions: Cell proliferationin hepatocellularcarcinoma all originating in the liver. Medical surgical removal. Four Ofcancer researchers or fewer mitoses per high power data from 282 patients with HCC and field of view was classified as low Ml and more than four collected mitotic index (Ml) for their as high Ml. The table calculatedthe tumours after shows data from this research. Variable I LowMl I HighMl A e/ ears I I LowMl I High Ml Female 88 80 39 mm 22 Tumoursize/ 26 133 101 small blood vessels 106 49 57 Invasionof No 70 metastasis 99 96 Intrahe atic No 31 Yes 56 recurrence < 2 ears 132 86 23 41 Earl No 75 74 Livercirrhosis 53 Yes 68 No 87 74 53 Yes 68 Hepatitis B or C Hepatitis B 111 107 No 23 15 5 Hepatitis C 21 1. Choose one of the variables on the table and test for an association with mitotic index, using the 2. Suggest reasons to account for the association, or chi- lack of association, between mitotic index and the squared test. Liaise with other students to ensure that variable that you chose. as many of the variables as possible are analysed. 3. Discuss with fellow students the conclusions for each of the variables that has been analysed. C Data-based questions: The principles of chemotherapy Chemotherapy is a treatment for cancer that involves the use of powerful drugs to destroy cancer cells by interfering with mitosis in these cells. Many of the side-effects of chemotherapy are related to the damage caused to normal cells as well as cancer cells. The graph depicts a generalized model of the impact of chemotherapy on the o number of normal and cancer cells. State the effect of chemotherapy on the number of cancer cells and normal cells. 2. Outline what happens in the interval between doses for both types of time 3. Distinguish etween the rate of recovery of normal cells and chemotherapy — normal cells — cancer cells cancer cei!f o r a bout of chemotherapy. 4. Suggest, reason, one specific side-effectof Figure 41 Effect of chemotherapy on numbers of chemotherao normal cells and cancer cells Linking questions What processes support the growth of organisms? a. Explain the role of the central vacuole in plant growth. (A2.2.8) b. Outline the role of photosynthesis in plant biomass production. (C4.2.15) c. Describe the role of mitosis and cytokinesis in the production of new cells. (D2.l.4) 2 How does the variation produced by sexual reproduction contribute to evolution? a. Explain how meiosis increases variation in a population. (D2.l.lI) b. Describe the process of evolutionby naturalselection.(A4.l.I) c. Outline the process of adaptive radiation.(A4.l.9)