Nanotoxicology Flashcards
Why are there concerns that nano materials have adverse health effects
Because of nanoparticles in environment that cause cardiovascular effects
Where in the lung might inhaled particles deposit?
Trachea
Bronchi
Alveoli
Can reach deep into lungs and can cross air spaces and get into vessels
What is the difference between alveoli type 1 cell AT1 and alveoli type 2 cells AT2
AT1 cells are stretched, flattened cells.
Cover 95% of alveolar surface.
Used for gas exchange
Susceptible to damage
AT2 5% of cells Secrete surfactant Divide and differentiate into AT1 cells Involved in alveolar fluid balance and host defence
What % of particles is uptaken by AT1 cells and AT2 cells
80% of AT1 cells internalise particles
20% of AT2 internalise
How do AT1 cells take up nanoparticles
Engulf the particles by clathrin- mediated endocytosis
Engulfed by clathrin coated pits and fuse with endosome
Can pass through plasma membrane
Describe how to set up an experiment to study bioactivity and toxicity of nanomaterial
Obtain cells
Incubate with nanomaterials at increasing dose
Collect medium after a certain time and measure cell mediators eg. Cytokines
Observe cells, look for particle uptake, DNA damage, cell viability
How do cells interact with silver
Silver spray products can be toxic, AT1 like cells
Nanofix-
Very toxic even at low conc
Kills all cells so no mediators produced
Diluent stimulates IL6, particles cause death
Mesofix-
Very little effect, combined or alone
How do cells interact with zinc
Zinc spray products, AT1 like cells
Therazinc-
Vehicle very toxic, particles less so
Dermazinc-
Particles and vehicle very toxic but less so
How do cells interact with copper
AT1 cells - CuO rods and spheres cytotoxic, spindles not
AT2 + macrophages- all shapes cytotoxic
How do cells interact with asbestos
Crocidolite - straight, strong, stays in lungs. Induces mesothelioma
Chrysotile - curly, frays, breaks up, cleared from lung. Induces fobrosis
Asbestos very similar in structure to carbon nanotubes
What is the effect of different length nanoparticles on human lung fibroblast activity
Short particles are slightly cytotoxic
As you increase length become more cytotoxic
Short particles induce more collagen release = fibrosis
Describe the concern due to similarity of asbestos and carbon nanotubes
Carbon nanotubes can exist in many formats
Long fibres of asbestos are worrysome
Can study long and short carbon nanotubes
Long particles can be very cytotoxic in some cell types
Longer C nanotubes more reactive with macrophages
Shorter C nanotubes more reactive with epithelial cells
How does the binding of surfactant proteins A and D to CNTs differ
Short particles adsorb surfactant protein A
Less of macrophages have to deal with infection
Could be a protective mechanism to coat CNTs
SPD is taken up by long particles
Bioreactivity of nanomaterials changes depending on location and what they adsorb
How does asbestos affect alveolar cells
Long particles have no effect in AT2 cells
But very cytotoxic in macrophages
Frustrated phagocytosis- macrophage engulfs long strand of asbestos