Radiobiologia - Mecanismos Celulares II Apoptose

Summary

The video discusses the biological mechanisms involved in radiation therapy, focusing on how radiation affects cellular processes. It explains how radiation induces DNA damage, leading to cell death or repair. Key topics include the stages of the cell cycle, DNA repair mechanisms, and the differences between tumor and normal tissue responses to radiation. The video also covers apoptosis, mitotic catastrophe, and the varying responses of different tissues to radiation, including rapid and delayed reactions. Understanding these processes is crucial for improving the effectiveness of radiotherapy while minimizing damage to healthy tissues.

Takeaways

• 😀 Radiation affects our cells by interfering with cell membranes, gene activation, and cell cycle processes, which can lead to repair or cell death.
• 😀 In radiotherapy, the goal is to destroy tumor tissue while preserving healthy tissue.
• 😀 Cells undergo a cycle with checkpoints, where they can halt progress to repair DNA damage before continuing division.
• 😀 The most sensitive phase in the cell cycle to radiation damage is the G2 phase and mitosis.
• 😀 Radiation-induced damage often leads to DNA double-strand breaks, which can trigger complex repair mechanisms or cell death.
• 😀 Cells can die after radiation exposure through mitotic death or genetic death, which involves lethal mutations affecting daughter cells.
• 😀 One key form of genetic death is known as mitotic catastrophe, where cells undergo abnormal mitosis, leading to micronuclei formation.
• 😀 Apoptosis, a form of programmed cell death, is one of the most studied responses to radiation, involving cell shrinkage, nuclear condensation, and phagocytosis.
• 😀 Cells can repair DNA damage through homologous recombination or non-homologous end joining, though the latter is error-prone.
• 😀 Different tissues respond differently to radiation: rapidly proliferating tissues exhibit acute responses, while slower proliferating tissues exhibit delayed effects.
• 😀 Tissues with lower proliferative activity, like muscles and bones, have a slower but repair-capable response to radiation, but they are more sensitive to exceeding their tolerance levels.

Q & A

What role does radiation play in affecting cells?

Radiation can affect cells in several ways, including interfering with the cell membrane, activating genes, and influencing the cell cycle. It can cause mutations, repairable lesions, or cell death. In radiotherapy, the goal is to destroy tumor tissue while preserving healthy tissue.

What is the cell cycle, and how does it relate to radiation damage?

The cell cycle consists of phases like G1, S (synthesis), G2, and mitosis. Radiation mainly affects cells during the G2 phase and mitosis, which are the most sensitive stages. The cycle is regulated by checkpoints that allow cells to repair damage before proceeding with division.

What happens when DNA damage occurs due to radiation?

When radiation causes DNA damage, particularly double-strand breaks, the cell detects the damage through sensors like ATM and NBS1. These proteins activate repair processes, allowing the cell to either repair the damage or stop the cycle to prevent faulty cell division.

What is the significance of the G2 and mitosis phases in response to radiation?

The G2 phase and mitosis are the most sensitive stages of the cell cycle in response to radiation. Radiation-induced DNA damage, especially double-strand breaks, is most likely to be lethal during these stages if the damage is not properly repaired.

What is 'mitotic catastrophe' and how does it relate to radiation-induced cell death?

Mitotic catastrophe is a form of cell death that occurs when a cell undergoes division after being damaged by radiation. The cell enters mitosis inappropriately and forms micronuclei, leading to lethal defects in the daughter cells, which cannot divide properly.

What is apoptosis, and how is it linked to radiation-induced cell death?

Apoptosis is programmed cell death. In response to radiation, certain genes like p53 favor apoptosis, leading to morphological changes in the cell, such as nuclear condensation and membrane breakdown. Apoptosis is often used as a mechanism to eliminate irreparably damaged cells.

How does the cell repair DNA damage after radiation exposure?

Cells repair DNA damage through mechanisms like homologous recombination and non-homologous end joining. Homologous recombination uses a sister chromatid as a template for accurate repair, while non-homologous end joining is a faster but error-prone repair process.

What is the difference between homologous recombination and non-homologous end joining in DNA repair?

Homologous recombination involves repairing DNA using a sister chromatid as a template, ensuring precise repair. Non-homologous end joining directly ligates broken DNA ends, which can lead to errors, such as insertions or deletions in the DNA sequence.

Why is it important to understand how normal tissues respond to radiation?

Understanding how normal tissues respond to radiation is crucial for radiotherapy planning. Different tissues react differently, with some having rapid responses (like skin and bone marrow) and others responding more slowly (like muscle and bone). This knowledge helps minimize damage to healthy tissues while maximizing tumor cell death.

What are the differences between acute and late responses to radiation in tissues?

Acute responses to radiation occur in tissues with high proliferative activity, such as skin and bone marrow, and manifest during or shortly after treatment. Late responses occur in tissues with low proliferative activity, like muscle and bone, and may take months or years to develop, often due to fibrosis or loss of tissue function.