Lesson 4 Flashcards
How can be classified cell death?
- accidental: caused by toxic agents
- programmed: it occurs during embryological development
Which are the main targets of lethal injuries?
- Inhibition of ATP synthesis
- Disruption of plasma membrane integrity
- Withdrawal of essential growth factors
Definition of blebbing
Fragmentation of the plasma membrane in spherical structures while the internal structure of the cell is degraded
How can you recognize an apoptotic cell?
Prior to death, apoptotic cells show:
- A very dense cytosol with normal or condensed mitochondria
- A normal or only slightly dilatated endoplasmic reticulum
- The nuclear chromatin is markedly clumped along the nuclear envelope and around the nucleolus.
- The nuclear contour is irregular and nuclear fragmentation occurs.
What is ‘oncosis’?
It’s a type of pre-lethal change in which the cell began to swell almost immediately after the injure occurred.
Definition and consequences of swelling
Swelling is an abnormal enlargement of a part of the body cell, typically as a result of an accumulation of fluid.
1- A swelling of the ER and Golgi and the formation of watery blebs around the cell surface.
2- The mitochondria undergo condensation and later it show high amplitude swelling because of damages to the inner mitochondrial membrane
3- Chromatin undergoes condensation and ultimately degradation
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Definition of necrosis
Series of changes that occur following cell death when the cell is converted to debris, they’re typically removed by the inflammatory response.
Which type of necrosis can be distinguished?
- Oncotic necrosis:
o It occurs in large zone or regionally in an organ after chemical toxicity
o It causes an inflammatory reaction, first acute and then chronic
o If the organism survive, dead cells are cleared away and there’s regeneration - Apoptotic necrosis
o Single cell basis
o Necrotic cells have an fragmented membranes and denatured proteins within the mitochondrial matrix. Ultimately, chromatin undergoes lysis
o Cathepsins, nucleolases and lipases clear away debris (they can survive the low pH of necrotic cells)
Which are the parameters which influence the probability of genetic damage?
- Level of exposure
- Distribution and retention of the chemical
- Efficiency of metabolic activation
- Efficiency of detoxification systems
- Reactivity of the chemical
- cell’s ability to repair or amplify the damage
- body ability to recognize and suppress the multiplication of aberrant cells
Explain some examples of chemicals that can exhibit genotoxicity in human cells
- Aromatic amines:
o They result also from diesel exhaust, combustion of wood and tobacco smoke.
o Their effect is carcinogenic and they’re pollutant. - Chlorinated hydrocarbons:
o They were used as pesticides (DDT).
o They have a strong carcinogenic and mutagenic effects - Aflatoxins
o They’re found in contaminated food (improperly stored or processed)
o Their effect is strongly carcinogenic - Nitrosamines: in meat, carcinogenic
- Polycyclic aromatic hydrocarbons:
o They derive from the process of organic compound, especially from the thermal decomposition in engines and incinerators
o Composed by multiple aromatic rings
o Pollutant - Nickel compounds:
o In stainless steel, batteries, mobile phones, water, soil, air, plants
o They can have carcinogenic or non-carcinogenic effects - chemotherapeutic agents
Which kind of damages can give the different genetic toxicant?
Small-scale mutations, such as point mutation, nonsense mutations, missense mutation, non-conservativemutation…
Large-scale mutations, such as aneuploidy or chromosome instability
Why is the Ames assay used?
The method tests the capability of the tested substance in creating mutations that can result in a return to a prototrophic state. It is used to detect the genetic toxicology effect.
Describe the Ames assay
Bacteria are spread on an agar plate with a small amount of histidine. When the histidine is depleted only bacteria that have mutated to gain the ability to produce its own histidine will survive. The plate is incubated for 48 hours, and the mutagenicity of a specific substance is proportional to the number of colonies that can be observed.
What is the MLA? Which is its role?
Mouse lymphoma TK assay (MLA) is an in vitro battery of tests designed to predict risk assessment prior in vivo testing.
The test has the potential to detect mutagenic and clastogenic events at the thymidine kinase locus of lymphoma TK cells by measuring resistance to the lethal nucleoside analogue trifluorothymidine.
