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Toxicology > unit 2 part 2 > Flashcards

unit 2 part 2 Flashcards

(82 cards)

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1
Q

most prevalent target

A

Nucleic Acid (DNA), proteins, and membranes

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2
Q

All ___________ compounds are potential targets

A

endogenous

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3
Q

Enzymes responsible for production of reactive metabolites should be _________

A

controlled

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4
Q

Practically irreversible (permanent), common with electrophilic toxicants and to a lesser degree with neutral free radicals

A

Covalent Binding

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5
Q

includes hydrophobic interactions, hydrogen bonding, and ionic bonding

A

NoncovalentBinding

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6
Q

Common in membrane and intracellular receptor, ion channels, and enzymes

A

NoncovalentBinding

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7
Q

common in neutral free radicals

A

Hydrogen Abstraction

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8
Q

Reactions include Hydrogen removal forming methylene (CH2) or Carbonyls (C=O), cross linking with DNA and other proteins

A

Hydrogen Abstraction

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9
Q

exchange of electrons, example oxidation of Ferrous to Ferric (methemoglobinemia)

A

Electron Transfer

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10
Q

only few toxin acts on this. Example include Diphtheria toxin - Elongation Factor 2

A

Enzymatic Reaction

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11
Q

Effects of Toxicant on Target Molecules

A
  1. Dysfunction of target molecules
  2. Destruction of Target Molecules
  3. NeoantigenFormation
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12
Q

Activation of protein target molecules
Mimicking endogenous ligand

A

Dysfunction of target molecules

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13
Q

Mimicking endogenous ligands may lead to
* Inhibition of __________
* Inhibition of __________
* Interfering with __________
* Alteration of__________

A
  • Inhibition of neurotransmitter receptor or ion channels
  • Inhibition of enzymes
  • Interfering with cytoskeleton dynamics
  • Alteration of protein conformation
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14
Q

Destruction of Target Molecules involves

A

Cross linking
Peroxidative degradation
DNA fragmentation

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15
Q

Covalent binding of xenobiotics to proteins may evoke an immune response

A

Neoantigen Formation

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16
Q

chemicals that bind to proteins spontaneously.

A

Dinitrochlorobenzene, penicillin, and nickel

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17
Q

Autooxidation to quinones

A

Neoantigen Formation

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18
Q

nzymatic biotransformations

A

Neoantigen Formation

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19
Q

Toxicity Not initiated by Reaction with Target Molecules (Alteration of the biologic microenvironment) includes

A
  1. Chemicals that alter Hydrogen ion concentration in the aqueous biophase
  2. Solvents and detergents that **alter the lipid phase **of cell membrane and destroying the solute gradient
  3. Xenobiotics that cause harm merely by occupying site or space.
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20
Q

(increase in cell number)

A

Hyperplasia

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21
Q

(increase in cell size)

A

Hypertrophy

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22
Q

(production of extracellular connective tissue)

A

Fibrosis

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23
Q

Toxic Alteration of Cellular Maintenance (Impairment of Internal Cellular Maintenance) Includes the following:

  1. Depletion of _____
  2. Sustained Rise of _____ _____ ion
  3. Overproduction of _____ and _____
A
  1. Depletion of ATP
  2. Sustained Rise of Intracellular Calcium ion
  3. Overproduction of ROS and RNS
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24
Q

plays an important role in cellular maintenance both for biosynthesis and source of energy

A

ATP

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25
required for muscular contraction and polymerization of the cytoskeleton, grueling cellular motility, cell division, vesicular transport, and maintenance of cell morphology
ATP
26
drives ion transporters (ATPases) to maintain cell function
ATP
27
leads to accumulation of ADP and depletion of ATP
Impairment of Oxidative Phosphorylation
28
Inhibition of hydrogen delivery to the Electron Transport Chain
Class A
29
Inhibition of electron transporting acting on/as 1. Inhibitors of electron transport complexes 2. Electron Acceptors
Class B
30
Inhibition of **oxygen delivery** to the electron transport chain
Class C
31
Inhibitor of **ADP phosphorylation** acting on/as
Class D
32
Chemical causing Mitochondrial damage and/or impaired transcription of key mitochondrial proteins
Class E
33
Ethanol and organic solvents ________(increase/decrease) membrane fluidity
increase
34
Lipid solvents destroy ________ membrane
plasma
35
Hydrocarbons destroy __________ membranes
lysosomal
36
Inhibition of hepatic synthesis of coagulation factors by coumarin is an example of
Impaired External Maintenance
37
____________ is regulated and maintained by impermeability to the plasma membrane and by a transport mechanism that removes Calcium ions from the cytoplasm
Calcium
38
Causes of Sustained elevation of cytosolic calcium: A. Chemicals inducing ____________ into the cytoplasm B. Chemicals inhibiting ___________ from the cytoplasm (inhibitors of Calcium-ATPase in cell membrane and/or endoplasmic reticulum)
Calcium ion influx; Calcium export
39
Via Ligand gated channels in neurons
Chemicals inducing Calcium ion influx into the cytoplasm
40
Via Voltage Gated channels
Chemicals inducing Calcium ion influx into the cytoplasm
41
Via Newly formed pores
Chemicals inducing Calcium ion influx into the cytoplasm
42
Across Disrupted cell membrane
Chemicals inducing Calcium ion influx into the cytoplasm
43
From Mitochondria
Chemicals inducing Calcium ion influx into the cytoplasm
44
Mechanism: From the endoplasmic reticulum
Chemicals inducing Calcium ion influx into the cytoplasm
45
Covalent binder: APAP, CCL4, chloroform
Chemicals inhibiting Calcium export from the cytoplasm
46
Thiol oxidants – diamide, HOOH
Chemicals inhibiting Calcium export from the cytoplasm
47
Cadmium, Vanadate,
Chemicals inhibiting Calcium export from the cytoplasm
48
Chemicals impairing mitochondrial ATP synthesis
Chemicals inhibiting Calcium export from the cytoplasm
49
Xenobiotics that can generate these (ROS and RNS) are ___________ and ___________
Redox cycles and Transition metals
50
Can be due to intracellular hypercalcemia and increased formation of peroxides
Overproduction of ROS and RNS
51
____________ helps generate ROS and RNS by activating dehydrogenases in the Citric acid cycle
Calcium
52
Types of Repair
1. MolecularRepair 2. CellularRepair 3. Tissue Repair
53
Oxidation of Thiols and Methylation of DNA are simply reversed
Molecular Repair
54
Hydrolytic Removal of the damaged molecule or insertion of newly synthesized unit
Molecular Repair
55
Resynthesis of the whole molecule
Molecular Repair
56
Needed in repair of lipids
reductants
57
Needed in repair of DNA
Chromatids
58
Needed in Direct Repair
DNA photolyase
59
Post-replication repair
Recombinational Repair
60
__________ of damaged cell organelles may be viewed as a universal mechanism of cellular repair
Autophagic Removal
61
Cellular repair for neurons
Clearance and regeneration of damaged axons
62
Regeneration of Damaged Axons is accompanied by
macrophages and Schwann Cells
63
In cells that can still proliferate, damage is repaired by ____________, followed by ___________
apoptosis or necrosis; proliferation
64
Active Deletion of damaged cells; initiated due to cellular injury
Apoptosis
65
regeneration of Tissue
Proliferation
66
Cell Adhesion molecules:
1) Cadherin 2) Connexins 3) Integrins
67
adjacent cells to adhere to one another
Cadherin
68
connect neighboring cells internally by association of these proteins into gap junctions
Connexins
69
link cells to the extra cellular matrix
Integrins
70
After injury of cells are detected, adjacent cells enter cell division cycle
Replacement of Lost Cells by Mitosis
71
___________ Cells (in G0) will enter G1 and progress mitosis.
Quiescent
72
Activation of stellate cells by platelet derived growth factor (PDGF) and transforming growth factor β (TGFβ). These growth factors are secreted by platelets at the site of injury.
Replacement of Extracellular Matrix
73
**Replacement of Extracellular Matrix**: Activation of ________________ by platelet derived growth factor (**PDGF**) and transforming growth factor β (**TGFβ**). These growth factors are secreted by________ at the site of injury.
stellate cells; platelets
74
Side Reactions to Tissue Injury
Inflammation Altered Protein Synthesis
75
Due to cytokines secreted by inflammatory cells such as resident macrophages.
* Inflammation
76
This process produces reactive oxygen and nitrogen species. Macrophages releases RNS and ROS during the process of tissue of injury
Inflammation
77
decreases tissue injury
Positive acute phase proteins
78
play important roles in the toxication and detoxification of xenobiotics
Negative acute phase proteins
79
increased tolerance of the organism to harm itself
Adaptation
80
Effects of adaptation: 1. ____________ delivery of the toxicant to the target 2. ____________ size or susceptibility of the target 3. _____________ capacity of the organism to repair itself 4. _______________ mechanisms to compensate the toxicant inflicted dysfunction.
1. Diminished delivery of the toxicant to the target 2. Decreased size or susceptibility of the target 3. Increased capacity of the organism to repair itself 4. Strengthened mechanisms to compensate the toxicant inflicted dysfunction.
81
Some injuries cannot be repaired due to the ___________ bonding of the toxican
covalently
82
High level of _________ impairs the electron transport chain
NAD+

Toxicology (9 decks)

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