Pathogenesis of cell injury – nuclear damage MCQs With Answer is an essential review for B. Pharm students studying mechanisms of nuclear injury, DNA damage, and their pharmacological implications. This concise guide covers nuclear changes in apoptosis and necrosis, DNA strand breaks, chromatin condensation, karyorrhexis, karyolysis, and key molecular players such as p53, caspases, ATM/ATR, and DNA repair pathways (NER, BER, HR, NHEJ). It also links oxidative stress, genotoxic drugs, radiation effects, biomarkers (γ-H2AX, TUNEL, comet assay), and laboratory detection methods relevant to drug safety and toxicology. Now let’s test your knowledge with 50 MCQs on this topic.
Q1. Which nuclear change is characterized by irreversible chromatin condensation into a small, dense mass during cell injury?
- Chromatin relaxation
- Pyknosis
- Karyolysis
- Karyorrhexis
Correct Answer: Pyknosis
Q2. Karyorrhexis refers to which nuclear event?
- Progressive dissolution of DNA
- Fragmentation of the nucleus
- Condensation into a dense mass
- Enlargement of nucleus
Correct Answer: Fragmentation of the nucleus
Q3. Karyolysis is best described as:
- Chromatin condensation
- Nuclear fragmentation into multiple pieces
- Dissolution of the nuclear structure and fading of chromatin
- Increase in nuclear size due to swelling
Correct Answer: Dissolution of the nuclear structure and fading of chromatin
Q4. Which enzyme is primarily responsible for internucleosomal DNA cleavage during apoptosis?
- Topoisomerase II
- Caspase-activated DNase (CAD)
- DNA polymerase I
- RNAse H
Correct Answer: Caspase-activated DNase (CAD)
Q5. The presence of a DNA “ladder” on agarose gel electrophoresis is characteristic of which process?
- Necrosis
- Apoptosis
- Autophagy
- Senescence without DNA fragmentation
Correct Answer: Apoptosis
Q6. γ-H2AX is a marker for which type of nuclear damage?
- Histone acetylation
- Double-strand DNA breaks
- Pyrimidine dimer formation
- RNA transcriptional activation
Correct Answer: Double-strand DNA breaks
Q7. Which DNA repair pathway primarily removes bulky helix-distorting lesions such as UV-induced pyrimidine dimers?
- Base excision repair (BER)
- Nucleotide excision repair (NER)
- Mismatch repair (MMR)
- Non-homologous end joining (NHEJ)
Correct Answer: Nucleotide excision repair (NER)
Q8. Which pathway repairs single-base lesions caused by oxidative damage or alkylation?
- Nucleotide excision repair (NER)
- Base excision repair (BER)
- Homologous recombination (HR)
- Mismatch repair (MMR)
Correct Answer: Base excision repair (BER)
Q9. Ionizing radiation induces which principal form of nuclear damage?
- Pyrimidine dimers
- Crosslinking of histones
- Single- and double-strand DNA breaks via free radicals
- Only base deamination
Correct Answer: Single- and double-strand DNA breaks via free radicals
Q10. Which protein is a key sensor and mediator of DNA damage responses, often called the “guardian of the genome”?
- NF-κB
- p53
- Akt
- Myc
Correct Answer: p53
Q11. Non-homologous end joining (NHEJ) repairs double-strand breaks by:
- Using a sister chromatid as template
- Direct ligation of DNA ends without a template
- Removing single bases
- Converting double strands to single strands
Correct Answer: Direct ligation of DNA ends without a template
Q12. Homologous recombination (HR) is most active during which cell cycle phase?
- G1 phase
- S/G2 phase when sister chromatids are available
- M phase
- G0 quiescent phase
Correct Answer: S/G2 phase when sister chromatids are available
Q13. Which assay detects DNA strand breaks at the single-cell level by electrophoresis of nucleoids?
- TUNEL assay
- Comet assay
- Western blot for histones
- Flow cytometry for CD markers
Correct Answer: Comet assay
Q14. TUNEL assay primarily detects:
- Protein crosslinks
- DNA fragmentation by labeling free 3’-OH ends
- Membrane phospholipid asymmetry
- Chromosomal translocations
Correct Answer: DNA fragmentation by labeling free 3’-OH ends
Q15. Micronuclei formation in cells is an indicator of:
- Effective DNA repair
- Genomic instability and chromosomal damage
- Increased mitochondrial function
- Enhanced transcriptional activity
Correct Answer: Genomic instability and chromosomal damage
Q16. Which staining method is specific for DNA and often used to visualize nuclear morphology?
- Feulgen stain
- Masson’s trichrome
- Oil Red O
- Periodic acid–Schiff (PAS)
Correct Answer: Feulgen stain
Q17. Which chemotherapeutic class causes DNA cross-linking leading to nuclear damage?
- Topoisomerase inhibitors
- Alkylating agents
- Antimetabolites
- Microtubule stabilizers
Correct Answer: Alkylating agents
Q18. Topoisomerase II inhibitors (e.g., doxorubicin, etoposide) mainly induce which nuclear lesion?
- Interstrand crosslinks only
- Double-strand DNA breaks by stabilizing cleavable complexes
- Pyrimidine dimers
- Telomere elongation
Correct Answer: Double-strand DNA breaks by stabilizing cleavable complexes
Q19. Which technique can detect sub-G1 population representing apoptotic cells with fragmented DNA?
- Immunohistochemistry for caspase-3
- Flow cytometry with DNA content analysis
- Western blot for histone H3
- Electron microscopy for mitochondria
Correct Answer: Flow cytometry with DNA content analysis
Q20. Oxidative stress primarily damages nuclear DNA by generating:
- Reactive oxygen species causing base modifications and strand breaks
- Excessive methylation only
- Protein phosphorylation in nucleoli
- Selective histone removal
Correct Answer: Reactive oxygen species causing base modifications and strand breaks
Q21. Which protein complex recognizes double-strand breaks and recruits repair proteins, activating cell cycle checkpoints?
- Ribosome
- MRN complex (Mre11-Rad50-Nbs1)
- Proteasome
- SNARE complex
Correct Answer: MRN complex (Mre11-Rad50-Nbs1)
Q22. Persistent DNA damage leading to irreversible cell cycle arrest is known as:
- Autophagy
- Cellular senescence
- Apoptotic fragmentation
- Necrotic swelling
Correct Answer: Cellular senescence
Q23. Which histone modification is commonly associated with DNA double-strand break signaling?
- Ubiquitination of tubulin
- Phosphorylation of H2AX (γ-H2AX)
- Acetylation of myosin
- Methylation of cytosolic proteins
Correct Answer: Phosphorylation of H2AX (γ-H2AX)
Q24. DNA mismatch repair (MMR) primarily corrects errors that occur during:
- Transcription
- DNA replication
- Homologous recombination
- RNA splicing
Correct Answer: DNA replication
Q25. Which cellular event often precedes nuclear fragmentation in apoptosis?
- Membrane rupture with inflammatory spillover
- Externalization of phosphatidylserine
- Immediate chromatin relaxation
- Telomerase activation
Correct Answer: Externalization of phosphatidylserine
Q26. Activation of which enzyme family is central to execution phase of apoptosis and subsequent nuclear disassembly?
- Kinases
- Caspases
- Phosphatases
- Polymerases
Correct Answer: Caspases
Q27. Which cellular organelle’s dysfunction commonly contributes to nuclear damage via release of pro-apoptotic factors?
- Golgi apparatus
- Mitochondria
- Lysosome only
- Peroxisome
Correct Answer: Mitochondria
Q28. Which of the following assays detects apoptotic cells by labeling DNA breaks with terminal deoxynucleotidyl transferase?
- Comet assay
- TUNEL assay
- ELISA for cytokines
- Southern blot
Correct Answer: TUNEL assay
Q29. Which nuclear change is reversible if the injurious stimulus is removed early?
- Severe karyolysis
- Early chromatin clumping and nuclear swelling
- Complete DNA fragmentation
- Permanent chromosomal deletions
Correct Answer: Early chromatin clumping and nuclear swelling
Q30. DNA crosslinking agents increase nuclear damage primarily by:
- Preventing strand separation needed for replication and transcription
- Increasing telomere length
- Enhancing mismatch repair efficiency
- Stimulating ribosomal biogenesis
Correct Answer: Preventing strand separation needed for replication and transcription
Q31. Which nuclear staining dye binds preferentially to A-T rich regions and is used in fluorescence microscopy?
- DAPI
- Sudan Black
- Alcian Blue
- Silver stain
Correct Answer: DAPI
Q32. Single-strand DNA breaks are most efficiently repaired by which mechanism?
- Homologous recombination
- Base excision repair (BER)
- Non-homologous end joining
- Mismatch repair
Correct Answer: Base excision repair (BER)
Q33. Which protein phosphorylation cascade is activated in response to replication stress and DNA damage?
- JAK-STAT pathway only
- ATM/ATR kinases and downstream Chk1/Chk2
- mTOR signaling only
- Wnt/β-catenin signaling
Correct Answer: ATM/ATR kinases and downstream Chk1/Chk2
Q34. DNA intercalating agents (e.g., actinomycin D) cause nuclear damage by:
- Binding between base pairs and disrupting replication/transcription
- Enhancing telomerase activity
- Specifically degrading ribosomal RNA
- Stabilizing microtubules
Correct Answer: Binding between base pairs and disrupting replication/transcription
Q35. Which nuclear phenomenon indicates irreversible cell injury and cell death due to loss of DNA staining?
- Hyperchromasia
- Karyolysis
- Pyknotic condensation
- Karyorrhexis
Correct Answer: Karyolysis
Q36. The comet assay tail length correlates with:
- Cell membrane composition
- Extent of DNA strand breaks
- Number of mitochondria
- Protein synthesis rate
Correct Answer: Extent of DNA strand breaks
Q37. Which of the following indicates a failure of DNA repair leading to mutagenesis and carcinogenesis?
- Efficient NER activity
- Accumulation of unrepaired DNA lesions and mutations
- Transient cell cycle arrest and repair
- Complete apoptosis of damaged cells
Correct Answer: Accumulation of unrepaired DNA lesions and mutations
Q38. Which nuclear protein binds to double-strand breaks to initiate repair and checkpoint signaling?
- Histone H1 only
- Ku70/Ku80 complex
- Actin
- Tubulin
Correct Answer: Ku70/Ku80 complex
Q39. DNA adduct formation by procarcinogens requires which process to become mutagenic?
- Direct repair by photolyase
- Metabolic activation to electrophilic intermediates
- Methylation by DNA methyltransferase exclusively
- Spontaneous conversion to RNA
Correct Answer: Metabolic activation to electrophilic intermediates
Q40. Which assay visualizes nuclear DNA fragmentation by labeling with fluorescent dUTP and terminal transferase?
- Comet assay
- TUNEL assay
- ELISPOT
- Bradford assay
Correct Answer: TUNEL assay
Q41. Which nuclear change is commonly assessed in toxicology as an index of genotoxicity using micronucleus test?
- Cell size increase
- Formation of small extranuclear bodies containing chromosomal fragments
- Glycogen accumulation
- Increased ribosomal RNA
Correct Answer: Formation of small extranuclear bodies containing chromosomal fragments
Q42. Caspase-3 activation leads to which nuclear event?
- Stabilization of nuclear envelope
- Cleavage of ICAD and activation of CAD causing DNA fragmentation
- Inhibition of endonucleases
- Repair of double-strand breaks
Correct Answer: Cleavage of ICAD and activation of CAD causing DNA fragmentation
Q43. Which nuclear surveillance mechanism eliminates cells with irreparable DNA damage to prevent propagation of mutations?
- Autophagy induction exclusively
- p53-mediated apoptosis or senescence
- Increased protein translation
- Telomerase activation
Correct Answer: p53-mediated apoptosis or senescence
Q44. Alkylating agents often target which DNA atom leading to miscoding and strand breaks?
- Ribose sugar hydroxyls only
- N7 of guanine and other nucleophilic sites
- Phosphate backbone exclusively
- Histone tails only
Correct Answer: N7 of guanine and other nucleophilic sites
Q45. Which method is used to detect γ-H2AX foci as an early indicator of double-strand breaks?
- Immunofluorescence microscopy using specific antibodies
- Mass spectrometry of lipids
- Periodic acid–Schiff histochemistry
- Transmission electron microscopy for ribosomes
Correct Answer: Immunofluorescence microscopy using specific antibodies
Q46. Telomere shortening contributes to nuclear damage primarily by:
- Triggering replicative senescence and genomic instability
- Increasing telomerase activity in all cells
- Enhancing homologous recombination only
- Preventing chromatin condensation
Correct Answer: Triggering replicative senescence and genomic instability
Q47. Which transcription factor is rapidly activated in response to DNA damage and can induce repair and cell-cycle arrest genes?
- HIF-1α
- p53
- NFAT
- STAT3
Correct Answer: p53
Q48. Which laboratory marker indicates apoptosis by detecting cleaved cytokeratin 18 or cleaved PARP?
- Alanine aminotransferase (ALT)
- Cleaved PARP or CK18 fragments measured by immunoassays
- Blood glucose
- Serum creatinine
Correct Answer: Cleaved PARP or CK18 fragments measured by immunoassays
Q49. Which of the following best differentiates apoptotic nuclear changes from necrotic nuclear changes?
- Apoptosis causes karyolysis while necrosis causes pyknosis
- Apoptosis shows organized chromatin condensation and fragmentation; necrosis shows karyolysis and swelling
- Both processes are identical morphologically
- Necrosis involves apoptotic bodies formation only
Correct Answer: Apoptosis shows organized chromatin condensation and fragmentation; necrosis shows karyolysis and swelling
Q50. In preclinical drug safety testing, which nuclear endpoint is commonly evaluated to assess genotoxic potential?
- Serum lipid profile
- Micronucleus test, comet assay, and chromosomal aberration tests
- Blood pressure measurement
- Urine specific gravity
Correct Answer: Micronucleus test, comet assay, and chromosomal aberration tests
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