Cytotoxicity and genotoxicity of nanoparticles

Describes the Cytotoxicity and genotoxicity of nanoparticles on exposure to the organisms.

1. Cytotoxicity and genotoxicity of nanoparticles M.S.KUMUTHAN 2018801301

2. INTRODUCTION Nanomaterials . Naturally occurring - viruses, biogenic magnetite, and ashes and particles from forest fires and active volcanoes Anthropogenic Unintentiona l - includes asbestos,metal or welding fume particles, and combustion by-products such as diesel exhaust particulate (DEP) and ultrafine particles (UFP ). Intentional -- nanotubes, nanowires, nanospheres , nanocrystals, fullerenes Dimensionality , morphology, composition,uniformity and agglomeration are the NPs classification criteria .NPs are spherical, tubular, irregular in shape and also exist in aggregated, agglomerated and fused.

3. Cytotoxicity of nanoparticles The plasma membrane as a lipid bilayer containing phospholipids with the hydrophilic head groups, and the hydrophobic tails, acts as a barrier to the passage of substances. Therefore materials for the crossing should have specific mechanisms. Three mechanisms are the most likely routes for NPs entry into cells.

4. Mechanism 1: NPs as small substances can move across the cell membrane by direct diffusion. However , the passage of NPs from the lipid bilayer depends on several factors such as size , charge , hydrophobicity, composition and shape. Diffusion of NPs across the plasma membrane can occur in certain situations . It should be noted that the characterization of the plasma membrane such as the lipid composition, fluidity and bounded molecular species are also important in passage of NPs from the cell membrane .

5. Mechanism 2: Endocytosis as second mechanism of nanoparticle entry is a pathway for internalizing solid or liquid particles. The plasma membrane creates a small deformation inward around the NPs that the deformation then pinches off a vesicle containing NPs from the membrane on the inside of the cell . The endocytosis can either be fluid phase or receptor mediated. In the fluid phase NPs diffuse into forming vesicles and enter through mass action, while in the solid phase the NPs can bind to a component of the cell surface such as membrane proteins, lipids or carbohydrates which will in turn be internalized carrying the substrate along into the cell.

6. Mechanism 3 : Channels and membrane transporter proteins are the third transmission mechanism which can mediate the translocation of NPs into cells. However , very specific features such as high level of selectivity , low open probability and small pore size are limiting factors for NPs entrance .

7. Nano-Zn fed. a. heart; b. liver; c. spleen; d. stomach; e. intestine . Nano-Fe fed. a. heart; b. liver; c. spleen; d. stomach; e. intestine. Nano-Si ( 10-20 nm) fed. a . heart; b. liver; c. spleen; d. stomach ; e. intestine. Micro-Si (45 μ m) fed. a. heart ; b.liver ; c. spleen; d. stomach; e.intestine

8. Toxicity mechanisms of NPs First, released toxic substances from NPs into exposure media. For instance, e.g. free Ag + ions from AgNPs or other toxic ions released from soluble NPs which could contribute to DNA damage. ROS generated through surface interactions with media. Direct physically interaction of NPs with biological targets, for instance e.g. carbon nanotube interaction with membranes or DNA. NPs can also interact with the mitochondria and other cell components and disrupt their functions.

9. Genotoxicity of nanoparticles Primary genotoxicity : Genotoxicity directly related to the exposure of the substance. Secondary genotoxicity :i s the result of the substance interacting with cells or tissues and releasing factors, which cause the adverse effects, such as inflammation and oxidative stress. The most common mechanistic scenario is that the particles interact with cells to induce ROS, which in turn lead to a cascade of effects, such as lysosomal membrane damage causing leakage of lytic enzymes, more ROS recruitment of inflammatory cells increased expression and all of which amplify the immune and inflammatory response.

10. M echanisms of genotoxicity Direct genotoxicity Direct genotoxicity results from physical interactions with DNA,for instance, influencing stacking forces among DNA bases, impacting phosphorylation, causing adduct formation, or altering gene expression/regulation. NPs that cross cellular and nuclear membranes through diffusion or endocytosis could interact directly with DNA by effect on replication, transcription or conformation in DNA structure either mechanically or by chemical binding to DNA, or during mitosis NPs reacts with chromosomes causing clastogenic (chromosomal break) or aneugenic effects (loss of chromosome) either mechanically or by chemical binding to DNA.

11. Indirect genotoxicity: Indirect genotoxicity NPs could interact with the nuclear proteins and not DNA (proteins involve in replication, transcription , or repair), or mitotic spindle (centrioles and microtubules) either mechanically or by chemical binding to proteins. The NPs also could disturb cell cycle checkpoints, interact with antioxidant enzyme or induce ROS generation by cell components either mechanically or by chemical binding to proteins and finally inhibition of protein activity and defect in cell cycle processes. Disruption or reduce in DNA repair function or increase in oxidative stress induced under ROS generated upon interaction with (e.g., mitochondria, cell membrane and etc.) resulting in antioxidant depletion, altered gene expression.

12. Inhibition of antioxidant defence Inhibition of antioxidants in vitro and consequent accumulation of reactive oxygen can potentially lead to DNA damage. For instance, interaction of NPs with glutathione as the major molecular antioxidant of cells. The silicon carbide NPs were associated with depletion of glutathione and inactivation of some antioxidant enzymes such as glutathione reductase and superoxide dismutase.

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