OxfordAQA International AS and A-level Biology: Cell division, mutation and cancer (9610)

This guide follows the OxfordAQA International AS and A-level Biology (9610) specification, Version 5.1 (International AS exams from May/June 2017, International A-level exams from May/June 2018). It covers sections 3.2.10 (cells divide by binary fission and mitosis) and 3.2.11 (mutation and cancer), plus Required practical 4. The specification places both sections in Unit 2, Biological systems and disease, which is listed under “International AS and A-level”; Units 3 and 4 are the International A-level only units.

After reading, condense with the revision notes and try the practice questions. The course hub is at OxfordAQA A-level Biology, the printable list is the checklist, and the free diagnostics help you decide where to begin.

What this unit covers

Section	What you must be able to do
3.2.10.1	Describe the cell cycle: interphase (G1, S, G2) and what happens in each phase
3.2.10.2	Describe mitosis and chromosome behaviour from interphase to telophase; explain the role of spindle fibres attached to centromeres; recognise stages in drawings or photographs
3.2.10.3	Describe binary fission, the fate of circular DNA and plasmids, and conjugation as horizontal gene transmission
3.2.11.1	Explain gene mutation, base deletion and substitution, mutagens, and the effect of the degenerate code; predict effects on amino acid sequences
3.2.11.2	Compare benign and malignant tumours; explain proto-oncogenes, tumour suppressor genes and oncogenes; interpret risk-factor data; link the cell cycle to anticancer drugs
Required practical 4	Make and observe stained root tip squashes; identify mitotic stages; calculate a mitotic index

3.2.10.1 The cell cycle

Eukaryotic cells that keep the ability to divide show a cell cycle. The period between one mitotic division and the next is interphase, which has three phases.

• G1: the cell grows, makes more protein and increases the number of organelles such as mitochondria and ribosomes.
• S phase: DNA is replicated, so each chromosome becomes two identical chromatids.
• G2: rapid cell growth and protein synthesis continue before division.

Mitosis is the division part of the cycle. Interphase is not a resting stage: most of the cell’s growth and all of its DNA replication happen there.

Worked example: how long does each phase last? In a culture of dividing cells, the whole cycle takes 20 hours. A sample of 500 cells is classified: 265 in G1, 125 in S, 70 in G2 and 40 in mitosis. Assume the cells are not synchronised, so the share of cells found in a stage matches the share of the cycle that stage occupies.

• G1: 265 / 500 = 53.0%, so 0.530 × 20 = 10.6 hours
• S: 125 / 500 = 25.0%, so 5.0 hours
• G2: 70 / 500 = 14.0%, so 2.8 hours
• Mitosis: 40 / 500 = 8.0%, so 1.6 hours

The four times add up to 20.0 hours, which is a useful check.

3.2.10.2 Mitosis

Mitosis produces two daughter cells, each with DNA identical to the parent cell. The spindle is made of fibres that attach to the centromere of each chromosome.

Stage	Chromosome behaviour	What to look for
Interphase	DNA already replicated; chromosomes are long, thin and not visible as separate structures	Nucleus with a visible boundary, often a nucleolus
Prophase	Chromosomes condense and become visible, each made of two chromatids joined at the centromere	Short, thick chromosomes scattered in the cell
Metaphase	Chromosomes line up across the middle of the cell, each centromere attached to spindle fibres	A single plate of chromosomes across the equator
Anaphase	Centromeres divide; spindle fibres shorten and pull the separated chromatids (now chromosomes) to opposite poles	Two sets of V-shaped chromosomes moving apart
Telophase	Chromosomes reach the poles and become less distinct; nuclear envelopes reform; the cell then divides in two	Two groups of chromosomes at opposite ends

The key point in anaphase is that spindle fibres attached to centromeres shorten and pull the chromatids apart. That is how each daughter nucleus gets one copy of every chromosome.

Worked example: counting chromosomes and chromatids. A body cell has 2n = 8 chromosomes.

• G1 cell: 8 chromosomes, each a single DNA molecule.
• After S phase (G2, prophase, metaphase): still 8 chromosomes, but each has two chromatids, so 16 chromatids.
• Anaphase: the 16 chromatids separate, so 16 chromosomes are moving, 8 towards each pole.
• Each daughter cell: 8 chromosomes, the same as the parent.

If the DNA mass of a G1 nucleus is 4.6 pg, it is 9.2 pg after S phase and 4.6 pg in each daughter cell. It never changes during mitosis itself; it halves only when the cell divides.

Recognising stages. Describe what you see rather than guess: are chromosomes visible? Are they in a line, in two groups, or scattered? A cell with a line of chromosomes across the middle is metaphase. Chromosomes in two groups near opposite sides, with a nucleus forming around each, are telophase. If they are still moving apart, with a V shape, it is anaphase.

3.2.10.3 Binary fission

Prokaryotic cells divide by binary fission:

1. The circular DNA is replicated.
2. Any plasmids are replicated.
3. The cytoplasm divides to give two daughter cells.

Each daughter cell has one copy of the circular DNA, but the number of plasmids may vary between cells. There is no spindle and no mitosis.

Conjugation. DNA can pass from one bacterium to another, even between species, during conjugation. One cell makes a thin connection to another, and a copy of a plasmid moves across. This is horizontal gene transmission, because genes move between living cells rather than from parent to offspring. It can spread a gene such as one for antibiotic resistance through a mixed population quickly.

Worked example: bacterial numbers. A culture starts with 40 cells and each divides every 20 minutes. In 3 hours there are 180 / 20 = 9 divisions. Number of cells = 40 × 2⁹ = 40 × 512 = 20 480.

3.2.11.1 Gene mutations

Any change in the base sequence of DNA is a gene mutation. Mutations arise spontaneously during DNA replication. Mutagens are physical or chemical agents that increase the frequency of mutations; ultraviolet light, ionising radiation and chemicals in tobacco smoke are examples.

• Base substitution: one base is replaced by another.
• Base deletion: one base is lost from the sequence.

The genetic code is degenerate: most amino acids are coded by more than one triplet. So a substitution may give a codon for the same amino acid and the protein does not change. A substitution may also change one amino acid, or change a codon to a stop codon so the chain ends early. A deletion shifts every triplet after the lost base, so the amino acids after that point usually all change.

Worked example: predicting the effect. Template strand: TAC CCT GAA TGT TTC GGA ATC. The mRNA is built from the template by complementary pairing (A with U, T with A, C with G, G with C).

mRNA: AUG GGA CUU ACA AAG CCU UAG. Amino acids: Met - Gly - Leu - Thr - Lys - Pro - stop.

• Substitution in the third base of codon 3 (CUU becomes CUG): CUG also codes for Leu, so the sequence is unchanged.
• Substitution in the first base of codon 3 (CUU becomes GUU): the codon now codes for Val. One amino acid changes; the rest are the same.
• Substitution in the first base of codon 5 (AAG becomes UAG): UAG is a stop codon, so the chain is Met - Gly - Leu - Thr only.
• Deletion of the fifth base of the mRNA sequence (the G of GGA, corresponding to a C on the template): reading in threes gives AUG GAC UUA CAA AGC CUU, which is Met - Asp - Leu - Gln - Ser - Leu. Four of the five amino acids after the first have changed; the third happens to be Leu again because UUA and CUU both code for it.

3.2.11.2 Mutations and cancers

A tumour is a lump of cells that has formed because division escaped normal control.

Feature	Benign tumour	Malignant tumour
Growth	Usually slow	Usually rapid
Boundary	Often surrounded by a capsule, so it stays in one place	No clear boundary; invades surrounding tissue
Spread	Stays at its site of origin	Cells detach, travel and found secondary tumours elsewhere
Cell appearance	Resemble the normal tissue cells	Often irregular, with a large nucleus and less like normal cells

Control of the cell cycle. The rate of cell division is controlled by two groups of genes:

• Proto-oncogenes stimulate cell division.
• Tumour suppressor genes slow cell division.

A mutation can turn a proto-oncogene into an oncogene, which stimulates cells to divide too quickly. A mutation can inactivate a tumour suppressor gene, so the brake on division is lost and the rate of division increases. Either way, uncontrolled division can produce a tumour.

Interpreting risk-factor data. The figures below are illustrative numbers supplied for this exercise, not survey results.

Cigarettes per day	Lung cancer cases per 100 000 people per year
None (never smoked)	14
1 to 9	62
10 to 19	118
20 or more	241

• Compare using a ratio: 241 / 14 = 17.2, so the 20-or-more group has about 17 times the incidence of the never-smoked group.
• The 10 to 19 group is 118 / 14 = 8.4 times higher.
• Incidence rises with each increase in smoking, so there is a positive correlation.
• Correlation alone does not prove cause. A fair evaluation notes whether groups were matched for age, sex and other factors, how smoking was measured, the sample sizes, and that a mechanism exists (mutagens in smoke damage DNA).

Cancer treatment and the cell cycle. Anticancer drugs often target dividing cells. Some stop DNA replication in S phase; others prevent the spindle forming, so mitosis cannot be completed. Cancer cells divide fast, so more of them are affected. Normal cells that divide often, such as hair follicle and gut lining cells, are also affected, which explains common side effects.

Required practical 4: root tip squash and mitotic index

A typical method:

1. Remove the last centimetre or so of a root that is actively growing.
2. Warm the tip in hydrochloric acid (about 1 mol dm⁻³) for a few minutes to soften the tissue.
3. Rinse the softened tip, lay it on a slide and drop on a stain that colours chromosomes, such as acetic orcein or toluidine blue.
4. Cover with a coverslip and squash gently to make a single layer of cells.
5. Observe with a light microscope and count the cells in each stage.

Safety: handle acid and stains with care; wear eye protection.

Mitotic index is the proportion of the cells you counted that were in mitosis: dividing-cell count over all cells seen, times 100 if you want a percentage.

Worked example. Five fields of view from one root tip:

Field	Total cells	Cells in mitosis
1	62	7
2	55	5
3	71	9
4	58	6
5	66	8

Total cells = 312 and cells in mitosis = 35. Mitotic index = 35 / 312 = 0.112, or 11.2%.

Pool all fields before dividing; do not average the five percentages. A larger count reduces the effect of chance. Count cells at the same distance from the tip each time, because the dividing region is just behind the tip.

Common errors

• Writing that DNA replicates in mitosis. It replicates in S phase.
• Saying chromosomes separate in metaphase. They line up in metaphase and separate in anaphase.
• Saying spindle fibres “cut” the chromosomes; they pull chromatids apart.
• Calling a frameshift a substitution. A deletion changes the reading frame; a substitution does not.
• Saying all substitutions change the protein, forgetting the degenerate code.
• Defining the mitotic index using only dividing cells as the denominator.

Official syllabus

Source: OxfordAQA, International AS and A-level Biology (9610), Version 5.1, International AS exams May/June 2017 onwards and International A-level exams May/June 2018 onwards, sections 3.2.10, 3.2.11 and Required practical 4.