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Toxicology > unit 2 part 2 > Flashcards

unit 2 part 2 Flashcards

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
Q

required for muscular contraction and polymerization of the cytoskeleton, grueling cellular motility, cell division, vesicular transport, and maintenance of cell morphology

A

ATP

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26
Q

drives ion transporters (ATPases) to maintain cell function

A

ATP

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27
Q

leads to accumulation of ADP and depletion of ATP

A

Impairment of Oxidative Phosphorylation

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28
Q

Inhibition of hydrogen delivery to the Electron Transport Chain

A

Class A

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29
Q

Inhibition of electron transporting acting on/as 1. Inhibitors of electron transport complexes
2. Electron Acceptors

A

Class B

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30
Q

Inhibition of oxygen delivery to the electron transport chain

A

Class C

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31
Q

Inhibitor of ADP phosphorylation acting on/as

A

Class D

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32
Q

Chemical causing Mitochondrial damage and/or impaired transcription of key mitochondrial proteins

A

Class E

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33
Q

Ethanol and organic solvents ________(increase/decrease) membrane fluidity

A

increase

34
Q

Lipid solvents destroy ________ membrane

A

plasma

35
Q

Hydrocarbons destroy __________ membranes

A

lysosomal

36
Q

Inhibition of hepatic synthesis of coagulation factors by coumarin is an example of

A

Impaired External Maintenance

37
Q

____________ is regulated and maintained by impermeability to the plasma membrane and by a transport mechanism that removes Calcium ions from the cytoplasm

A

Calcium

38
Q

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)

A

Calcium ion influx; Calcium export

39
Q

Via Ligand gated channels in neurons

A

Chemicals inducing Calcium ion influx into the cytoplasm

40
Q

Via Voltage Gated channels

A

Chemicals inducing Calcium ion influx into the cytoplasm

41
Q

Via Newly formed pores

A

Chemicals inducing Calcium ion influx into the cytoplasm

42
Q

Across Disrupted cell membrane

A

Chemicals inducing Calcium ion influx into the cytoplasm

43
Q

From Mitochondria

A

Chemicals inducing Calcium ion influx into the cytoplasm

44
Q

Mechanism: From the endoplasmic reticulum

A

Chemicals inducing Calcium ion influx into the cytoplasm

45
Q

Covalent binder: APAP, CCL4, chloroform

A

Chemicals inhibiting Calcium export from the cytoplasm

46
Q

Thiol oxidants – diamide, HOOH

A

Chemicals inhibiting Calcium export from the cytoplasm

47
Q

Cadmium, Vanadate,

A

Chemicals inhibiting Calcium export from the cytoplasm

48
Q

Chemicals impairing mitochondrial ATP synthesis

A

Chemicals inhibiting Calcium export from the cytoplasm

49
Q

Xenobiotics that can generate these (ROS and RNS) are ___________ and ___________

A

Redox cycles and Transition metals

50
Q

Can be due to intracellular hypercalcemia and increased formation of peroxides

A

Overproduction of ROS and RNS

51
Q

____________ helps generate ROS and RNS by activating dehydrogenases in the Citric acid cycle

A

Calcium

52
Q

Types of Repair

A
  1. MolecularRepair
  2. CellularRepair
  3. Tissue Repair
53
Q

Oxidation of Thiols and Methylation of DNA are simply reversed

A

Molecular Repair

54
Q

Hydrolytic Removal of the damaged molecule or insertion of newly synthesized unit

A

Molecular Repair

55
Q

Resynthesis of the whole molecule

A

Molecular Repair

56
Q

Needed in repair of lipids

A

reductants

57
Q

Needed in repair of DNA

A

Chromatids

58
Q

Needed in Direct Repair

A

DNA photolyase

59
Q

Post-replication repair

A

Recombinational Repair

60
Q

__________ of damaged cell organelles may be viewed as a universal mechanism of cellular repair

A

Autophagic Removal

61
Q

Cellular repair for neurons

A

Clearance and regeneration of damaged axons

62
Q

Regeneration of Damaged Axons is accompanied by

A

macrophages and Schwann Cells

63
Q

In cells that can still proliferate, damage is repaired by
____________, followed by ___________

A

apoptosis or necrosis; proliferation

64
Q

Active Deletion of damaged cells; initiated due to cellular injury

A

Apoptosis

65
Q

regeneration of Tissue

A

Proliferation

66
Q

Cell Adhesion molecules:

A

1) Cadherin
2) Connexins
3) Integrins

67
Q

adjacent cells to adhere to one another

A

Cadherin

68
Q

connect neighboring cells internally by association of these proteins into gap junctions

A

Connexins

69
Q

link cells to the extra cellular matrix

A

Integrins

70
Q

After injury of cells are detected, adjacent cells enter
cell division cycle

A

Replacement of Lost Cells by Mitosis

71
Q

___________ Cells (in G0) will enter G1 and progress mitosis.

A

Quiescent

72
Q

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.

A

Replacement of Extracellular Matrix

73
Q

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.

A

stellate cells; platelets

74
Q

Side Reactions to Tissue Injury

A

Inflammation
Altered Protein Synthesis

75
Q

Due to cytokines secreted by inflammatory cells such as resident macrophages.

A
  • Inflammation
76
Q

This process produces reactive oxygen and nitrogen species. Macrophages releases RNS and ROS during the process of tissue of injury

A

Inflammation

77
Q

decreases tissue injury

A

Positive acute phase proteins

78
Q

play important roles in the toxication and detoxification of xenobiotics

A

Negative acute phase proteins

79
Q

increased tolerance of the organism to harm itself

A

Adaptation

80
Q

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.

A
  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
Q

Some injuries cannot be repaired due to the ___________ bonding of the toxican

A

covalently

82
Q

High level of _________ impairs the electron transport chain

A

NAD+

Toxicology (9 decks)

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