Genotoxicity, carcinogenicity, teratogenicity, and mutagenicity MCQs With Answer

Introduction: Understanding genotoxicity, carcinogenicity, teratogenicity, and mutagenicity is essential for B. Pharm students studying pharmacology and toxicology. This concise guide introduces core concepts—DNA damage, mutation types, chromosomal aberrations, prenatal developmental toxicity, and mechanisms leading to cancer—while linking in vitro and in vivo assays used in risk assessment. Key topics include the Ames test, micronucleus and comet assays, rodent carcinogenicity bioassays, metabolic activation, dose–response relationships, and regulatory guidelines for safety evaluation. You will learn to distinguish genotoxic from non‑genotoxic carcinogens, recognize teratogenic windows, and apply assays like chromosomal aberration and HPRT mutation tests to drug safety evaluation. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. What is the best definition of genotoxicity?

• The ability of agents to damage DNA or chromosomal structure
• The capacity of a compound to cause cell death by necrosis
• The potential of a substance to alter protein folding
• The tendency of a drug to induce allergic reactions

Correct Answer: The ability of agents to damage DNA or chromosomal structure

Q2. Mutagenicity refers to which of the following?

• The induction of permanent changes in DNA sequence
• The enhancement of cellular repair mechanisms
• The suppression of oncogene expression
• The inhibition of mitochondrial respiration

Correct Answer: The induction of permanent changes in DNA sequence

Q3. Carcinogenicity is best described as:

• The ability of an agent to cause cancer in an organism
• The reversible inhibition of cell proliferation
• The induction of transient oxidative stress without long-term effects
• The promotion of immune tolerance to pathogens

Correct Answer: The ability of an agent to cause cancer in an organism

Q4. Teratogenicity refers to:

• The ability to cause congenital malformations during embryogenesis
• The capacity to induce carcinomas in adults
• The potential to produce reversible behavioral changes
• The induction of acute liver toxicity only

Correct Answer: The ability to cause congenital malformations during embryogenesis

Q5. The primary purpose of the Ames test is to:

• Detect mutagenic potential using Salmonella strains
• Measure chromosomal breakage in mammalian bone marrow
• Assess teratogenic risk in pregnant animals
• Quantify tumor incidence in 2-year rodent studies

Correct Answer: Detect mutagenic potential using Salmonella strains

Q6. The micronucleus assay primarily detects:

• Chromosomal fragments or whole chromosomes not included in the daughter nuclei
• Single base substitutions in bacterial DNA
• Changes in mitochondrial DNA copy number
• Serum biomarkers of hepatic injury

Correct Answer: Chromosomal fragments or whole chromosomes not included in the daughter nuclei

Q7. The comet assay is mainly used to detect:

• Single- and double-strand DNA breaks at the single cell level
• Whole-organism teratogenic outcomes
• Long-term tumor development in rodents
• Protein crosslinking within chromatin

Correct Answer: Single- and double-strand DNA breaks at the single cell level

Q8. What distinguishes a clastogen from an aneugen?

• Clastogens cause chromosome breaks; aneugens cause mis-segregation of whole chromosomes
• Clastogens only affect mitochondrial DNA; aneugens affect nuclear DNA
• Clastogens induce point mutations; aneugens cause oxidative base modifications
• Clastogens are non-genotoxic promoters; aneugens are genotoxic initiators

Correct Answer: Clastogens cause chromosome breaks; aneugens cause mis-segregation of whole chromosomes

Q9. Why is metabolic activation important in genotoxicity testing?

• Many pro-mutagens require bioactivation (e.g., hepatic S9) to form DNA-reactive metabolites
• It prevents false positives by detoxifying compounds before testing
• It measures direct binding of compounds to plasma proteins
• It simulates chronic exposure conditions in humans

Correct Answer: Many pro-mutagens require bioactivation (e.g., hepatic S9) to form DNA-reactive metabolites

Q10. DNA adducts are:

• Covalent attachments between chemicals and DNA bases that can initiate mutations
• Noncovalent interactions of drugs with membrane lipids
• Protein aggregates formed during oxidative stress
• Transient RNA secondary structures during transcription

Correct Answer: Covalent attachments between chemicals and DNA bases that can initiate mutations

Q11. The HPRT mutation assay in mammalian cells detects mutations by selecting for resistance to:

• 6-thioguanine
• Amikacin
• Penicillin
• Cyclosporine

Correct Answer: 6-thioguanine

Q12. Standard rodent carcinogenicity bioassays commonly run for approximately:

• Two years (24 months)
• Two weeks
• Three months
• Five years

Correct Answer: Two years (24 months)

Q13. Which statement correctly contrasts genotoxic and non-genotoxic carcinogens?

• Genotoxic carcinogens directly damage DNA; non-genotoxic act by epigenetic or proliferative mechanisms
• Genotoxic carcinogens only act in bacteria; non-genotoxic act only in mammals
• Genotoxic carcinogens are always teratogens; non-genotoxic carcinogens are never teratogens
• Genotoxic carcinogens require chronic inflammation to cause tumors; non-genotoxic do not

Correct Answer: Genotoxic carcinogens directly damage DNA; non-genotoxic act by epigenetic or proliferative mechanisms

Q14. The critical window for teratogenic effects in humans is mainly during:

• Organogenesis, approximately weeks 3–8 of embryonic development
• The late third trimester only
• Postnatal infancy exclusively
• Gametogenesis in elderly individuals

Correct Answer: Organogenesis, approximately weeks 3–8 of embryonic development

Q15. The Ames test uses Salmonella typhimurium strains that are auxotrophic for which amino acid?

• Histidine
• Lysine
• Methionine
• Proline

Correct Answer: Histidine

Q16. The role of a positive control in genotoxicity assays is to:

• Confirm the assay is capable of detecting known genotoxic agents
• Demonstrate the test compound is safe for humans
• Increase the mutation rate of test strains for sensitivity
• Replace the need for negative controls

Correct Answer: Confirm the assay is capable of detecting known genotoxic agents

Q17. The in vitro chromosomal aberration assay primarily detects:

• Structural chromosomal changes in cultured mammalian cells
• Point mutations in bacterial genes
• Systemic immunotoxic effects in rodents
• Protein misfolding in the endoplasmic reticulum

Correct Answer: Structural chromosomal changes in cultured mammalian cells

Q18. A point mutation is best described as:

• A single base substitution in DNA
• A large chromosomal deletion spanning multiple genes
• An extra whole chromosome (trisomy)
• A crosslink between DNA and proteins

Correct Answer: A single base substitution in DNA

Q19. Which assay has highest sensitivity for detecting low levels of DNA strand breaks in individual cells?

• Comet assay
• Standard bacterial reverse mutation assay
• Two-year rodent bioassay
• In vitro receptor-binding assay

Correct Answer: Comet assay

Q20. In micronucleus assays performed in mammals, micronuclei are commonly scored in which cell type to indicate recent damage?

• Polychromatic erythrocytes
• Hepatocytes
• Neurons
• Keratinocytes

Correct Answer: Polychromatic erythrocytes

Q21. The S9 mix used in in vitro genotoxicity testing is prepared from:

• Rat (or hamster) liver microsomal fraction to provide metabolic activation enzymes
• Human plasma to supply growth factors
• Mouse brain homogenate for neuronal enzymes
• Plant extracts to inhibit metabolism

Correct Answer: Rat (or hamster) liver microsomal fraction to provide metabolic activation enzymes

Q22. According to IARC classification, an agent is Group 1 when there is:

• Sufficient evidence of carcinogenicity in humans
• No evidence of carcinogenicity in any species
• Evidence only in vitro but not in vivo
• Limited mechanistic information available

Correct Answer: Sufficient evidence of carcinogenicity in humans

Q23. A recommended genotoxicity testing battery for a new drug typically includes:

• In vitro bacterial reverse mutation, in vitro mammalian cell assay, and in vivo micronucleus or comet assay
• Only a 2-year rodent carcinogenicity study
• Clinical trials without preclinical genotoxicity data
• Only acute toxicity testing in one species

Correct Answer: In vitro bacterial reverse mutation, in vitro mammalian cell assay, and in vivo micronucleus or comet assay

Q24. Which of the following is a classical human teratogen known to cause limb defects?

• Thalidomide
• Aspirin at therapeutic doses
• Paracetamol (acetaminophen)
• Caffeine at low intake

Correct Answer: Thalidomide

Q25. For genotoxic carcinogens, many regulatory approaches assume which dose–response relationship?

• A linear, no-threshold model for cancer risk at low doses
• A high-threshold model where any dose below threshold is safe
• An inverse dose–response where low doses are more toxic
• No relationship between dose and effect

Correct Answer: A linear, no-threshold model for cancer risk at low doses

Q26. Oxidative DNA damage commonly produces which lesion often measured as a biomarker?

• 8-oxoguanine (8-oxo-dG)
• Thymidine dimers exclusively
• Protein carbonylation only
• RNA methylation markers

Correct Answer: 8-oxoguanine (8-oxo-dG)

Q27. A likely cause of false-negative results in the Ames test is:

• Absence of metabolic activation when a compound is a pro-mutagen
• Use of an excessively high concentration of positive control
• Scoring revertants too frequently
• Using histidine-rich medium for plating

Correct Answer: Absence of metabolic activation when a compound is a pro-mutagen

Q28. Aneuploidy refers to:

• An abnormal number of chromosomes in a cell
• A specific point mutation in the P53 gene
• Only structural chromosomal deletions
• The formation of DNA adducts exclusively

Correct Answer: An abnormal number of chromosomes in a cell

Q29. Mutagenic potency in experimental systems is most commonly reported as:

• Mutation frequency per number of cells or per locus tested
• Median lethal dose (LD50) in humans
• Time to onset of clinical symptoms in weeks
• Serum concentration required to inhibit growth by 50%

Correct Answer: Mutation frequency per number of cells or per locus tested

Q30. Which regulatory guideline specifically addresses genotoxicity testing of pharmaceuticals?

• ICH S2(R1)
• ICH Q3A
• ICH E14
• ICH M7 only for impurities

Correct Answer: ICH S2(R1)

G S Sachin

I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.

Mail- Sachin@pharmacyfreak.com