Radiobiology 7 MCQ
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Questions and Answers

What is a major source of reactive oxygen species/reactive nitrogen species in irradiated cells?

  • Radiolysis of water and nitric oxide synthase activation (correct)
  • Oxidation of fatty acids
  • Excessive protein degradation
  • Mitochondrial dysfunction

What effect does peroxynitrite anion (ONOO−) have in cells?

  • It causes extensive depurinations in DNA (correct)
  • It enhances the activity of antioxidants
  • It only reacts with nucleotides
  • It is chemically inert to cellular targets

Which compound helps to mitigate the damaging effects of free radicals in cells?

  • Glutathione (correct)
  • Amifostine
  • Hydroxyl radical
  • Peroxynitrite

How are DNA damages from metabolic reactive oxygen species typically characterized compared to radiation-induced damage?

<p>Random distribution versus clustered distribution (A)</p> Signup and view all the answers

What is one role of manganese superoxide dismutase (MnSOD) in the cell?

<p>Converts superoxide radicals into molecular oxygen (A)</p> Signup and view all the answers

What is the significance of thiol-containing drugs like Amifostine in the context of radiotherapy?

<p>They protect normal tissues from radiation damage. (B)</p> Signup and view all the answers

Which type of damage does ionizing radiation specifically target?

<p>DNA primarily (B)</p> Signup and view all the answers

What common characteristic do the reactive oxygen species generated during irradiation and those produced during normal metabolism share?

<p>They have similarities in their generation sources. (B)</p> Signup and view all the answers

Which reactive species is notably produced by the reaction of nitric oxide with superoxide anion?

<p>Peroxynitrite (D)</p> Signup and view all the answers

What cellular process is disrupted when DNA double-strand breaks occur?

<p>Cell-cycle progression (D)</p> Signup and view all the answers

Which phase of the cell cycle involves DNA replication?

<p>S phase (A)</p> Signup and view all the answers

What is the primary role of cyclin-dependent kinases (CDKs) in the cell cycle?

<p>Controlling the order of cell-cycle events (C)</p> Signup and view all the answers

Which of the following CDKs is associated with a diagnostic value in breast cancers?

<p>CDK1 (C)</p> Signup and view all the answers

What pathway is NOT involved in the rejoining of DNA double-strand breaks?

<p>Base excision repair (D)</p> Signup and view all the answers

Which phase of the cell cycle is mitosis followed by cytokinesis?

<p>M phase (A)</p> Signup and view all the answers

What effect does ionizing radiation primarily have when cells are exposed during mitosis?

<p>Induces chromosomal rearrangements (D)</p> Signup and view all the answers

Which checkpoint controls the transition between the G2 and M phases?

<p>G2 checkpoint (B)</p> Signup and view all the answers

What specific role does CDK5 play in cancer pathology?

<p>Plays a role in lung cancer development (A)</p> Signup and view all the answers

Which type of aberrations reflects the cell-cycle phase at the time of irradiation?

<p>Chromosomal aberrations (A)</p> Signup and view all the answers

What is the estimated range of DNA breaks resulting from one gray of absorbed radiation dose?

<p>500 to 1000 single-strand and 25 to 50 double-strand breaks (D)</p> Signup and view all the answers

Which of the following describes local multiply damaged sites (LMDS)?

<p>Clusters of ionizations resulting in complex DNA lesions. (D)</p> Signup and view all the answers

How does high LET irradiation differ from low LET irradiation in terms of DNA damage?

<p>High LET irradiation causes increased numbers and complexities of DNA clustered lesions. (A)</p> Signup and view all the answers

What role do reactive oxygen species (ROS) may play in the cellular response to ionizing radiation?

<p>They activate the ceramide-sphingomyelin pathway, potentially leading to apoptosis. (C)</p> Signup and view all the answers

What is a consequence of chromosomal rearrangements following irradiation?

<p>They may contribute to the carcinogenic properties of ionizing radiation. (A)</p> Signup and view all the answers

What effect do agents that alter protein function have on radiation-induced apoptosis?

<p>They can modify the level of apoptosis, affecting cell survival. (A)</p> Signup and view all the answers

Which of the following factors increase the complexity of DNA clustered lesions?

<p>The presence of reactive oxygen species and high LET irradiation. (D)</p> Signup and view all the answers

Which statement is true about DNA repair pathways in relation to clustered lesions?

<p>Multiple DNA repair pathways likely work together to repair clustered lesions. (C)</p> Signup and view all the answers

What range of ionizations is estimated to occur within a diploid cell per gray of absorbed radiation dose?

<p>Approximately 105 ionizations. (A)</p> Signup and view all the answers

Flashcards

Ionization

The process of removing an electron from an atom, leading to the formation of an ion.

DNA Damage

Molecular damage caused by radiation, including DNA breaks and base modifications.

Local Multiply Damaged Sites (LMDS)

Regions within DNA where multiple damage events occur in close proximity, leading to a greater impact.

DNA Repair Pathways

The ability of cells to repair DNA damage and maintain genetic stability.

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High LET Irradiation

Radiation with high linear energy transfer (LET) deposits energy densely, leading to more complex DNA damage that is harder to repair.

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Reactive Oxygen Species (ROS)

Reactive oxygen species (ROS) are molecules with unpaired electrons, causing damage to various cellular components, including proteins.

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Apoptosis

A process of programmed cell death triggered by various stimuli, including radiation.

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Ceramide-Sphingomyelin Pathway

A cell signaling pathway involved in apoptosis, activated by ROS damage to the cell membrane.

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Chromosomal Rearrangements

Unstable chromosomes with abnormal arrangements, such as translocations, deletions, or amplifications.

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Chromosomal Instability

Increased rate of chromosomal aberrations and genetic instability, often observed after exposure to radiation.

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Radiation vs. Metabolic DNA Damage

Radiation-induced damage to DNA often occurs in clusters, while metabolic damage spreads randomly.

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How are RNS formed?

Reactive Nitrogen Species (RNS) like peroxynitrite are formed when nitric oxide (NO) reacts with superoxide radicals.

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Impact of Peroxynitrite

Peroxynitrite is a highly reactive molecule that can damage key cellular components like lipids, proteins, and DNA.

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Why is DNA a major target for radiation?

Radiation can lead to changes in any molecule within a cell, but DNA is a prime target due to its crucial role in cell function.

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Cellular Defense Against Free Radicals

The cell uses antioxidants like glutathione, vitamins C and E, and enzymes like MnSOD to combat the damaging effects of free radicals.

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Why is DNA damage from radiation so dangerous?

Radiation-induced DNA damage can be lethal to the cell, even in small amounts.

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Radiation's Impact on Nitric Oxide Production

Ionizing radiation activates inducible nitric oxide synthase, leading to the production of nitric oxide (NO).

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The Reactivity of Nitric Oxide

Nitric oxide (NO) is relatively inert but reacts with superoxide to form peroxynitrite, a highly reactive RNS.

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Effects of Radiation on the Cell

The random nature of radiation means that damage can occur in any molecule within a cell. The cell uses a variety of strategies to protect itself from this damage, including the use of antioxidants and repair mechanisms.

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Protecting Normal Tissues During Radiation Therapy

The use of thiol-containing drugs like Amifostine can help protect normal tissues from the damaging effects of radiation therapy.

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Chromosomal Rearrangements and Radiation

DNA double-strand breaks can lead to chromosomal rearrangements during the first cell division after exposure to ionizing radiation. The type of chromosome aberration observed depends on the phase of the cell cycle when the radiation occurred.

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Cell Cycle

The cell cycle is a series of events that takes place in a cell leading to its growth and division. It consists of four phases: G1, S, G2, and M.

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G1 Phase

G1 phase is the first stage of the cell cycle, where the cell grows and duplicates its cellular contents.

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S Phase

S phase is a crucial part of the cell cycle where DNA replication occurs. Each of the 46 chromosomes (23 pairs) is duplicated by the cell.

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G2 Phase

G2 phase is the preparation stage for cell division. The cell checks for any errors in the replicated DNA and prepares for mitosis.

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M Phase

M phase encompasses both mitosis (nuclear division), where the copied chromosomes are separated, and cytokinesis (cell separation) leading to the formation of two identical daughter cells.

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Cell Cycle Checkpoints

Molecular 'checkpoint' genes play a crucial role in regulating the cell cycle. They ensure the correct order of events and prevent any errors or mistakes.

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Cyclin-Dependent Kinases (CDKs)

Cyclin-dependent kinases (CDKs) are a family of enzymes that regulate cell cycle progression. They are activated by cyclins, which are proteins that bind to CDKs and activate their kinase activity.

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CDKs and Cancer

Studies have shown that certain Cyclin-dependent kinases (CDKs) are linked to specific types of cancer. For example, CDK1 is associated with esophageal and breast cancers, CDK5 with lung cancer, and CDK6 with ovarian cervix cancer. These findings highlight the importance of CDKs in cancer development.

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Study Notes

Generation of Reactive Nitrogen Species

  • Ionizing radiation stimulates inducible nitric oxide synthase (NOS) activity, increasing nitric oxide (NO) production.
  • NO is chemically inert to most cellular components except heme.
  • NO reacts with O2 to form peroxynitrite anion (ONOO-).
  • The peroxynitrite anion is highly reactive, damaging lipids, thiols, proteins, and DNA.
  • Water radiolysis and early activation of nitric oxide synthases are major sources of reactive oxygen and nitrogen species (ROS/RNS) in irradiated cells, particularly with ambient oxygen present.

ROS/RNS Role in Carcinogenesis

  • ROS/RNS damage DNA and biomolecules.
  • Damage can lead to oncogene activation (growth factors) and suppression of tumor genes.
  • This leads to genetic instability, triggering inflammation, cellular transformation, differentiation, proliferation, and promoting tumor growth.
  • Angiogenesis, immune response, tissue invasion/metastasis are also affected.
  • Cell cycle repair and death, specifically apoptosis, senescence, and autophagy, are responses involved in this process.

Endogenous and Radiation-Induced DNA Alterations

  • Endogenous biochemical processes contribute significantly to genome mutations.
  • ROS produced during normal metabolic processes (especially O2 and H2O2) cause extensive depurination and depyrimidination.
  • Radiation-induced ROS are similar to metabolically generated ROS in their overall spectrum.
  • However, radiation-induced DNA damage clusters more frequently than metabolically-induced damage.

Cellular Antioxidants

  • Cells contain naturally occurring thiol compounds (e.g., glutathione, cysteine, cysteamine, and metallothionein).
  • Sulfhydryl (SH) groups in these compounds can react with free radicals, lessening their damage.
  • Other key antioxidants include vitamins C and E and intracellular manganese superoxide dismutase (MnSOD).
  • MnSOD catalyzes superoxide radicals into more stable molecular oxygen (02).

Intracellular Thiols and Antioxidants in Radiotherapy

  • Intracellular thiols and antioxidant levels differ between normal and tumor tissues.
  • Manipulating these levels may protect normal tissues from radiotherapy damage.
  • Amifostine, a thiol-containing drug, protects against radiation-induced xerostomia (dry mouth) after salivary gland irradiation.

DNA Damage by Ionizing Radiation

  • The random nature of energy deposition during irradiation means damage can occur in any cell molecule.
  • DNA is a primary target due to its biological importance.
  • Even small amounts of DNA damage can cause cell death (lethality).
  • Estimated ionization events in a typical diploid cell following irradiation are in the 105 range per Gray (unit of absorbed radiation dose).
  • Different types of DNA damage include cross-links, damaged bases, single-strand breaks, and double-strand breaks.
  • Most ionization events do not result in DNA damage.

Focal Areas of DNA Damage

  • "Local multiply damaged sites" (LMDS) arise from the clustering of ionizations within a few nanometers of DNA.
  • Combinations of single- or double-strand breaks, altered or lost bases, and DNA-DNA or DNA-protein crosslinks are features of these sites.
  • Repair mechanisms struggle with clustered lesions.
  • High LET (Linear Energy Transfer) irradiation causes more complex and numerous clustered lesions, making repair more challenging.

Cell Cycle and Irradiation

  • The cell cycle has specific phases (G1, S, G2, M).
  • Irradiation in different phases results in varying mitotic delays.
  • Cells irradiated during specific phases experience more significant cell death rates as compared to others.
  • Cell cycle progression is regulated by cyclin-dependent kinases (CDKs).

Immunohistochemical Study of Cyclin-Dependent Kinases (CDKs)

  • CDK1 is important in diagnosing esophageal and breast cancers.
  • CDK5 is linked to lung cancers while CDK6 is implicated in ovarian cancer.
  • These findings have implications in the treatment and diagnosis strategy.

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Description

Explore the role of reactive nitrogen species (RNS) and reactive oxygen species (ROS) in the process of carcinogenesis. This quiz covers how ionizing radiation affects nitric oxide production and leads to DNA damage, oncogene activation, and tumor progression. Test your knowledge on the mechanisms involved in these complex biological processes.

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