Mechanisms of Toxicity Flashcards
The severity of a toxicant depends, in large part, on the concentration of the toxicant at its site of action. Which of the following will decrease the amount of toxicant reaching its site
of action?
a. absorption across the skin.
b. excretion via the kidneys.
c. toxication.
d. reabsorption across the intestinal mucosa.
e. discontinuous endothelial cells of hepatic sinusoids.
Answer: b. excretion via the kidneys
Explanation: Excretion removes the toxicant from the body, decreasing its concentration at the site of action. Other options involve absorption or redistribution which do not decrease toxicant levels.
Toxication (or metabolic activation) is the biotransformation of a toxicant to a more toxic and reactive species. Which of the following is not a reactive chemical species commonly formed by toxication?
a. electrophiles.
b. nucleophiles.
c. superoxide anions.
d. hydroxy radicals.
e. hydrophilic organic acids.
Answer: e. hydrophilic organic acids
Explanation: These are generally end products of detoxification, not reactive intermediates. The others (electrophiles, radicals, etc.) are classic reactive species.
Which of the following is not an important step in detoxication of chemicals?
a. formation of redox-active reactants.
b. reduction of hydrogen peroxide by glutathione peroxidase.
c. formation of hydrogen peroxide by superoxide dismutase.
d. reduction of glutathione disulfide (GSSG) by glutathione reductase (GR).
e. conversion of hydrogen peroxide to water and molecular oxygen by catalase.
Answer: a. formation of redox-active reactants
Explanation: Detoxification aims to neutralize/react with these species, not form them.
Regarding the interaction of the ultimate toxicant with its target molecule, which of the
following is false?
a. Toxicants often oxidize or reduce their target molecules, resulting in the formation of a
harmful by-product.
b. The covalent binding of a toxicant with its target molecule permanently alters the
target’s function.
c. The noncovalent binding of a toxicant to an ion channel irreversibly inhibits ion flux
through the channel.
d. Abstraction of hydrogen atoms from endogenous compounds by free radicals can result
in the formation of DNA adducts.
e. Several toxicants can act enzymatically on their specific target proteins.
Answer: c. The noncovalent binding of a toxicant to an ion channel irreversibly inhibits ion flux through the channel.
Explanation: Noncovalent interactions are reversible by nature. Irreversibility implies covalent binding.
All of the following are common effects of toxicants on target molecules EXCEPT:
a. blockage of neurotransmitter receptors.
b. interference with DNA replication due to adduct formation.
c. cross-linking of endogenous molecules.
d. opening of ion channels.
e. mounting of an immune response.
Answer: e. mounting of an immune response
Explanation: This is more of a secondary, systemic response, not a direct molecular interaction like the others listed.
a. blockage of neurotransmitter receptors
→ Very common effect — classic for neurotoxins and drugs.
b. interference with DNA replication due to adduct formation
→ Definitely common — many genotoxic compounds act this way.
c. cross-linking of endogenous molecules
→ Seen in many alkylating agents and toxins.
d. opening of ion channels
→ Some toxins (like tetrodotoxin, veratridine) act specifically by modifying ion channels.
e. mounting of an immune response
→ This is a systemic reaction, not a direct molecular interaction on the target molecule. It’s a downstream physiological consequence, not a mechanism of molecular toxicity.
Which of the following proteins functions to prevent the progression of the cell cycle?
a. NF-κB.
b. MAPK.
c. CREB.
d. c-Myc.
e. IκB.
Answer: e. IκB
Explanation: IκB inhibits NF-κB, a transcription factor that promotes survival and proliferation.
Which of the following would have the largest negative impact on intracellular ATP levels?
a. moderately decreased caloric intake.
b. interference with electron delivery to the electron transport chain.
c. inability to harvest ATP from glycolysis.
d. increased synthesis of biomolecules.
e. active cell division.
Answer: b. interference with electron delivery to the electron transport chain
Explanation: This blocks oxidative phosphorylation, the major ATP source.
What happens when a toxicant induces elevation of cytoplasmic calcium levels?
a. Mitochondrial uptake of calcium dissipates the electrochemical gradient needed to
synthesize ATP.
b. Formation of actin filaments increases the strength and integrity of the cytoskeleton.
c. It decreases the activity of intracellular proteases, nucleases, and phospholipases.
d. The cell becomes dormant until the calcium is actively pumped from the cell.
e. The generation of reactive oxyg
Answer: a. Mitochondrial uptake of calcium dissipates the electrochemical gradient needed to synthesize ATP
Explanation: High calcium in mitochondria leads to ATP synthesis failure and possibly apoptosis.
Cytochrome c is an important molecule in initiating apoptosis in cells. All of the following
regarding cytochrome c are true EXCEPT:
a. The release of cytochrome c into the cytoplasm is an important step in apoptosis
initiation.
b. The loss of cytochrome c from the electron transport chain blocks ATP synthesis by
oxidative phosphorylation.
c. Loss of cytochrome c from the inner mitochondrial membrane results in increased
formation of reactive oxygen species.
d. Bax proteins mediate cytochrome c release.
e. Caspases are proteases that increase cytoplasmic levels of cytochrome c.
Answer: e. Caspases are proteases that increase cytoplasmic levels of cytochrome c
Explanation: Caspases are activated by cytochrome c; they don’t increase its levels.
All of the following regarding DNA repair are true EXCEPT:
a. In a lesion that does not cause a major distortion of the double helix, the incorrect base
is cleaved and the correct base is inserted in its place.
b. Base excision repair and nucleotide excision repair are both dependent on a DNA
polymerase and a DNA ligase.
c. In nucleotide excision repair, only the adduct is cleaved, and the gap is then filled by
DNA polymerase.
d. Pyrimidine dimers can be cleaved and repaired directly by DNA photolyase.
e. Recombinational repair requires that a sister strand serves as a template to fill in
missing nucleotides.
Answer: d. Pyrimidine dimers can be cleaved and repaired directly by DNA photolyase
Explanation: Humans lack DNA photolyase — they use nucleotide excision repair instead.
a. TRUE
→ Describes base excision repair: minor helix distortion, glycosylase removes the damaged base, then DNA pol/ligase fill and seal the gap.
b. TRUE
→ Both base and nucleotide excision involve DNA polymerase + ligase to repair the site after excision.
c. FALSE (correct answer)
→ This is inaccurate: In nucleotide excision repair, a short segment of DNA (not just the adduct) is excised (usually 24–32 nucleotides), not just the adduct. The excision includes flanking nucleotides to ensure full removal of distortion.
d. TRUE in some organisms (but NOT humans)
→ DNA photolyase is present in bacteria, yeast, and some plants/animals, but not in humans. However, if this question is asking about general DNA repair across species, it could be considered true.
(This is where confusion often arises.)
e. TRUE
→ Homologous recombination uses the sister chromatid as a template — totally accurate.
Apoptosis can serve as a tissue repair process in a number of cell types. In which of the
following cell types would this be a plausible mechanism of tissue repair?
a. female germ cells.
b. gastrointestinal epithelium.
c. neurons.
d. retinal ganglion cells.
e. cardiac muscle cells.
Answer: b. gastrointestinal epithelium
Explanation: These cells are rapidly dividing and regularly replaced, making apoptosis part of normal maintenance and repair.
Which of the following is NOT associated with carcinogenesis?
a. mutation.
b. normal p53 function.
c. Ras activation.
d. inhibition of apoptosis.
e. DNA repair failure.
Answer: b. normal p53 function
Explanation: p53 prevents carcinogenesis by triggering apoptosis or cell cycle arrest in damaged cells.
