Biology • Year 12 • Module 6 • Lesson 2
Mutagens — How Genetic Damage Is Increased
Apply the mutagen-vs-mutation distinction to real dose-response data, real exposure tables, and a scenario about radiotherapy. Practise reading mutagen mechanism off a graph and explaining it back in HSC verbs.
1. Interpret a dose-response curve for ionising radiation
The figure below shows the relative frequency of chromosomal aberrations (a marker of DNA damage that can become a mutation) in cultured human lymphocytes irradiated with X-rays at increasing doses. Two curves are shown — one when DNA repair systems are functional, one when repair is chemically inhibited. 8 marks
Figure 1.1. Relative chromosomal aberrations per cell in cultured human lymphocytes following X-ray exposure. Stylised data after Cornforth & Bedford (1987), Radiation Research 111: 385–405.
1.1 Describe the trend in chromosomal aberrations as X-ray dose increases, for each curve. 2 marks
1.2 At a dose of 2 Gy, estimate the relative frequency of aberrations on each curve and state the approximate difference between the two. 2 marks
1.3 Explain, using lesson terminology, why the repair-functional curve has a shallow "shoulder" at low doses but the repair-inhibited curve does not. 2 marks
1.4 Use this graph to justify the lesson's claim that "exposure to a mutagen increases the risk of mutation but does not guarantee one." 2 marks
2. Interpret a mutagen-exposure table
The table below shows results from a classic Ames test-style investigation. Four agents were tested for mutagenicity in Salmonella typhimurium; each plate was scored for the number of "revertant" bacterial colonies (a higher count = more mutations induced by the agent than would arise spontaneously). 8 marks
| Agent tested | Lesson category | Dose | Mean revertant colonies per plate (n=3) |
|---|---|---|---|
| None (control) | — | 0 | 22 |
| Distilled water | Negative control | 0.1 mL | 24 |
| UV light | Radiation | 30 sec exposure | 148 |
| X-ray | Radiation | 1.5 Gy | 372 |
| 2-aminopurine (a base analogue) | Chemical | 50 µg/plate | 295 |
| Background radiation simulation | Natural | 0.01 Gy (over 24 h) | 41 |
Stylised data after Ames, McCann & Yamasaki (1975), Mutation Research 31: 347–364.
2.1 Identify the agent with the greatest mutagenic effect and the agent with the smallest mutagenic effect (above background). State both colony counts. 2 marks
2.2 Calculate the fold-increase in revertant colonies caused by X-ray compared with the no-agent control. Show your working. 2 marks
2.3 Using lesson content, explain why X-ray exposure produced more revertants than UV at the doses tested, even though both are radiation. 2 marks
2.4 The "background radiation simulation" plate still scored above the negative control. Use this row to evaluate the common student claim that "natural radiation isn't really a mutagen." 2 marks
3. Apply to a new scenario — radiotherapy collateral damage
A patient is receiving targeted X-ray radiotherapy to treat a localised tumour. The radiation oncologist explains that, while the X-rays are aimed at cancer cells, neighbouring healthy cells will also receive a smaller dose. The patient asks the oncologist why healthy cells in the path of the beam don't all become mutated and turn into new cancers. 6 marks
3.1 Using lesson terminology, identify the type of mutagen the patient is being exposed to and the dominant mechanism of DNA damage involved. 2 marks
3.2 Explain to the patient — in two cause-and-effect steps — why exposure to a mutagen does not always cause mutation. 2 marks
3.3 Predict and justify what would happen if a hypothetical patient had a genetic condition that disabled their DNA repair systems. 2 marks
Q1.1 — Trend description (2 marks)
Both curves show that chromosomal aberrations rise as X-ray dose increases — i.e. ionising radiation behaves as a mutagen in a dose-dependent way [1]. The repair-inhibited curve rises steeply and almost linearly from 0 to 4 Gy; the repair-functional curve rises more gradually, with a shallow "shoulder" at low doses (0–1 Gy) before steepening [1].
Q1.2 — Estimate at 2 Gy (2 marks)
At 2 Gy, the repair-inhibited curve sits at approximately 0.75 aberrations per cell (relative units) [1]; the repair-functional curve sits at approximately 0.20 aberrations per cell — a difference of roughly 0.5–0.55 units in favour of the repair-functional cells [1]. Accept ±0.1.
Q1.3 — Why the shoulder exists (2 marks)
At low doses, the number of DNA strand breaks induced is small enough that the cell's DNA repair systems can correct most damage before it is copied during replication, so few of the breaks become permanent chromosomal aberrations — producing the shallow "shoulder" [1]. When repair is inhibited, every break caused by the mutagen is more likely to persist and be fixed into the sequence, so even the lowest doses translate directly into aberrations and no shoulder appears [1].
Q1.4 — Mutagen exposure ≠ guaranteed mutation (2 marks)
The two curves at the same dose give different aberration frequencies — at 2 Gy the repair-functional cells have about a quarter as many aberrations as the repair-inhibited cells [1]. This confirms the lesson's claim: an X-ray dose increases the risk of mutation, but whether damage becomes a permanent mutation depends on whether DNA repair acts before replication. Exposure is necessary but not sufficient for mutation [1].
Q2.1 — Greatest and smallest mutagenic effect (2 marks)
Greatest: X-ray, 372 colonies/plate [1]. Smallest (above background): background radiation simulation, 41 colonies/plate — still measurably above the 22-colony control [1].
Q2.2 — Fold-increase for X-ray (2 marks)
Fold-increase = 372 ÷ 22 = ≈ 16.9-fold increase relative to the no-agent control [1 for working, 1 for correct answer]. Accept 16–17.
Q2.3 — Why X-ray > UV in this test (2 marks)
UV radiation typically causes abnormal bonding between neighbouring bases (e.g. pyrimidine dimers), distorting the DNA but leaving the backbone largely intact [1]. X-rays are ionising radiation — they have enough energy to remove electrons and to break one or both DNA strands. Strand breaks are more severe damage and are harder for repair systems to handle perfectly, so a higher proportion are fixed as revertant mutations at comparable exposures [1].
Q2.4 — Background radiation as a mutagen (2 marks)
The background-radiation plate (41 colonies) is roughly double the negative control (22), confirming that even low-dose, naturally occurring ionising radiation acts as a mutagen [1]. The lesson's point is reinforced: "natural" does not mean "harmless" — what matters is the mechanism (low-dose ionising damage) and the exposure, not whether the source feels natural [1].
Q3.1 — Identify the mutagen and mechanism (2 marks)
The patient is being exposed to ionising radiation (specifically X-rays) — a radiation mutagen from the lesson [1]. The dominant mechanism of DNA damage is removal of electrons from atoms in or around the DNA, producing strand breaks (single- and double-strand) and severe DNA damage [1].
Q3.2 — Two-step explanation for the patient (2 marks)
Step 1: A mutagen (X-rays) causes DNA damage — but damage is not yet a mutation [1]. Step 2: DNA repair systems can correct that damage before the cell next replicates its DNA. Only if the damage is left unrepaired and then copied during replication does it become a lasting mutation in a cell lineage [1].
Q3.3 — Patient with disabled repair (2 marks)
With DNA repair disabled, a far higher proportion of X-ray-induced strand breaks would persist into the next replication cycle and be fixed as permanent mutations [1]. This patient would therefore have a much higher mutation rate from the same X-ray dose, raising the risk of secondary cancers — consistent with the steeper repair-inhibited dose-response curve in Q1 [1].