Mutagenicity testing MCQs With Answer

Mutagenicity testing MCQs With Answer

Introduction: Mutagenicity testing is a core component of the biological evaluation of drug therapy, aiming to identify chemical or physical agents that can cause changes in genetic material. For M.Pharm students, mastering mutagenicity concepts, test systems, regulatory expectations, and interpretation of results is essential for preclinical safety assessment and risk management. This quiz set focuses on key assays (Ames, micronucleus, comet, mammalian cell mutation tests), test design elements (metabolic activation, controls, dose selection), and regulatory guidance. The questions are designed to deepen understanding, reinforce practical knowledge, and prepare students for exam and research scenarios in drug development.

Q1. What is the primary purpose of mutagenicity testing in drug development?

• To measure acute toxicity in humans
• To detect chemical agents that cause genetic alterations such as gene mutations and chromosomal damage
• To evaluate pharmacokinetics and drug metabolism pathways
• To determine maximum tolerated dose in animals

Correct Answer: To detect chemical agents that cause genetic alterations such as gene mutations and chromosomal damage

Q2. The bacterial reverse mutation (Ames) test commonly uses which organisms?

• Saccharomyces cerevisiae strains
• Salmonella typhimurium strains
• Human lymphocyte cultures
• V79 Chinese hamster lung cells

Correct Answer: Salmonella typhimurium strains

Q3. What is the role of the S9 metabolic activation mix in genotoxicity assays?

• It provides nutrients to support bacterial growth
• It supplies mammalian metabolic enzymes (e.g., liver microsomal enzymes) to convert promutagens into active metabolites
• It acts as a staining agent for DNA visualization
• It inhibits DNA repair to increase mutation detection

Correct Answer: It supplies mammalian metabolic enzymes (e.g., liver microsomal enzymes) to convert promutagens into active metabolites

Q4. Which Salmonella strain is primarily used to detect frameshift mutations in the Ames test?

• TA100
• TA98
• TA1535
• TA1537

Correct Answer: TA98

Q5. The cytokinesis-block micronucleus assay is most useful for detecting which types of genetic damage?

• Only single base pair substitutions
• Chromosome breaks (clastogenicity) and whole chromosome loss (aneugenicity)
• Mitochondrial DNA mutations
• Transient enzymatic inhibition

Correct Answer: Chromosome breaks (clastogenicity) and whole chromosome loss (aneugenicity)

Q6. The comet assay (single-cell gel electrophoresis) primarily measures which endpoint?

• Chromosome number changes by karyotyping
• DNA strand breaks and alkali-labile sites at the single-cell level
• Mutation frequency at the HPRT locus
• Protein adduct formation

Correct Answer: DNA strand breaks and alkali-labile sites at the single-cell level

Q7. Which OECD test guideline corresponds to the bacterial reverse mutation (Ames) test?

• OECD 488
• OECD 471
• OECD 476
• OECD 474

Correct Answer: OECD 471

Q8. The HPRT assay in mammalian cells is designed to detect which type of genetic event?

• Chromosome mis-segregation only
• Gene mutations at the hypoxanthine-guanine phosphoribosyltransferase locus
• DNA strand breaks measured by electrophoresis
• Epigenetic methylation changes

Correct Answer: Gene mutations at the hypoxanthine-guanine phosphoribosyltransferase locus

Q9. In the cytokinesis-block micronucleus assay, which agent is used to block cytokinesis so that binucleated cells can be scored?

• Colchicine
• Cytochalasin B
• Actinomycin D
• Mitomycin C

Correct Answer: Cytochalasin B

Q10. How do clastogens differ from aneugens in their mechanism of action?

• Clastogens induce whole chromosome loss; aneugens cause point mutations
• Clastogens cause DNA strand breaks and structural chromosome aberrations; aneugens interfere with chromosome segregation causing aneuploidy
• Clastogens only act in bacteria; aneugens only act in mammals
• Clastogens inhibit metabolic enzymes while aneugens activate them

Correct Answer: Clastogens cause DNA strand breaks and structural chromosome aberrations; aneugens interfere with chromosome segregation causing aneuploidy

Q11. What is the primary purpose of including a positive control in a genotoxicity assay?

• To reduce assay costs
• To demonstrate the assay’s sensitivity and that the test system can detect a genotoxic effect
• To neutralize the test compound
• To increase cell proliferation

Correct Answer: To demonstrate the assay’s sensitivity and that the test system can detect a genotoxic effect

Q12. The mouse lymphoma assay (TK± locus) is useful for detecting what kind of genetic damage?

• Only mitochondrial DNA damage
• Forward gene mutations and small deletions at the thymidine kinase locus
• Large chromosomal rearrangements exclusively
• Protein synthesis inhibition

Correct Answer: Forward gene mutations and small deletions at the thymidine kinase locus

Q13. Which ICH guideline specifically addresses genotoxicity testing strategies for pharmaceuticals?

• ICH S7A
• ICH S2(R1)
• ICH Q3C
• ICH E14

Correct Answer: ICH S2(R1)

Q14. Which statement best reflects the conventional view about threshold dose-response for direct DNA-reactive mutagens?

• Direct DNA-reactive mutagens are generally considered to have a safe threshold below which there is no risk
• Direct DNA-reactive mutagens are typically assumed to have no safe threshold and any exposure carries some risk
• All mutagens follow a hormetic beneficial effect at low doses
• Threshold concepts are irrelevant in regulatory genotoxicity assessment

Correct Answer: Direct DNA-reactive mutagens are typically assumed to have no safe threshold and any exposure carries some risk

Q15. When selecting test concentrations for an in vitro mammalian cell genotoxicity assay, what is a common practical criterion for the highest concentration?

• The highest concentration should produce at least 80–90% cell proliferation
• The highest concentration should produce measurable cytotoxicity but not excessive cell death (commonly targeting around 50% reduction in viability as a guideline)
• The highest concentration must equal the solubility limit in dimethyl sulfoxide only
• No cytotoxicity is allowed at any test concentration

Correct Answer: The highest concentration should produce measurable cytotoxicity but not excessive cell death (commonly targeting around 50% reduction in viability as a guideline)

Q16. What does a “revertant colony” in the Ames test indicate?

• The test strain has acquired antibiotic resistance
• A mutation has occurred restoring the ability to synthesize the required amino acid (reversion to prototrophy)
• Complete cell lysis has occurred
• Metabolic activation failed in the assay

Correct Answer: A mutation has occurred restoring the ability to synthesize the required amino acid (reversion to prototrophy)

Q17. An in vivo comet assay is particularly useful for which of the following reasons?

• It can measure point mutations in a specific gene in blood only
• It allows detection of DNA strand breaks in specific tissues of dosed animals, providing tissue-target information
• It replaces all in vitro assays and is sufficient alone for regulatory submission
• It primarily measures chromosomal translocations by metaphase analysis

Correct Answer: It allows detection of DNA strand breaks in specific tissues of dosed animals, providing tissue-target information

Q18. Sister chromatid exchange (SCE) frequency is increased by agents that interfere with which process, and which labeling method is commonly used to visualize SCEs?

• SCEs reflect mitochondrial dysfunction and are visualized by DAPI staining
• SCEs indicate increased recombination during DNA replication and are visualized using bromodeoxyuridine (BrdU) incorporation and differential staining
• SCEs are signs of protein misfolding and are detected by immunohistochemistry
• SCEs measure RNA transcription errors and use ethidium bromide staining

Correct Answer: SCEs indicate increased recombination during DNA replication and are visualized using bromodeoxyuridine (BrdU) incorporation and differential staining

Q19. Which factor is a common cause of false-positive results in in vitro genotoxicity assays?

• Use of appropriate positive controls
• Excessive cytotoxicity or precipitation of the test compound
• Inclusion of metabolic activation systems like S9
• High assay reproducibility

Correct Answer: Excessive cytotoxicity or precipitation of the test compound

Q20. If a new chemical yields a positive result in an in vitro genotoxicity battery, what is the typical regulatory next step?

• Immediately approve the compound for clinical trials
• Conduct follow-up in vivo genotoxicity testing (e.g., in vivo micronucleus or comet assay) to assess relevance and risk
• Discard the in vitro data and repeat the same in vitro tests indefinitely
• Assume the finding is irrelevant and proceed with marketing

Correct Answer: Conduct follow-up in vivo genotoxicity testing (e.g., in vivo micronucleus or comet assay) to assess relevance and risk

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