Mechanisms of Toxicology 2

Question 1

three destinies a cell can take

Answer 1

division
differentiation
apoptosis

Question 2

the nature of primary cellular dysfunction caused by toxicants depends on the role of the ____

Answer 2

target molecule

Question 3

if the target molecule is involved in cellular regulation____

Answer 3

dysregulation of gene expression and/or dysregulation of momentary cellular function occur

Question 4

if the target molecule is involved in the cell’s internal maintenance…

Answer 4

the dysfunction can compromise the survival of the cell

Question 5

when two receptors receive a molecule such as a hormone

Answer 5

dimerization

Question 6

what are two things that can happen for dysregulation of transcription

Answer 6

interaction with the transcription factor

change of response element

Question 7

Receptor activation ultimately leads to

Answer 7

1. altered gene expression that increases or decrease the quantity of a specific protein
2. causes a chemical modification of a protein

Question 8

can repress translation of mRNA into proteins, regulating protein synthesis posttranscriptionally

Answer 8

microRNA

Question 9

Transcription of genetic information from DNA to mRNA and miRNA is largely controlled by

Answer 9

interplay between TFs and regulatory promoter region of genes

Question 10

Xenobiotics may interact with TFs ….

Answer 10

altering the promoter region of the gene

Question 11

in addition to altering the fate of specific cells, compounds that act on ligand activated TFs can also evoke change in

Answer 11

the metabolism of endobiotics and xenobiotics by inducing overexpression of relevant enzymes

Question 12

increased promotor methylation by a toxicant can

Answer 12

silence genes

Question 13

decreased methylation by a toxicant can

Answer 13

activate more genes

Question 14

protein protein interactions are called

Answer 14

dimerization

Question 15

causes phosphorylation

Answer 15

protein kinase

Question 16

causes dephosphorylation

Answer 16

protein phosphatase

Question 17

proliferative effects in the dyregulation of signal transduction

Answer 17

activate protein kinase or deactivate phosphatase

Question 18

antiproliferative effects of dysregulation of signal transduction

Answer 18

inhibit kinase

Question 19

critical biochemical disorders that cause alteration of cellular maintenance

Answer 19

ATP depletion
calcium accumulation
ROS/RNA generation

Question 20

xenobiotics that facilitate phosphorylation of signal transducers often promote

Answer 20

mitosis or tumor formation

Question 21

chemicals may alter synaptic levels of neurotransmitters by

Answer 21

interfering with their synthesis, storage, release, or removal from the vicinity of the receptor

Question 22

plays a central role in cellular maintenance both as a chemical for biosynthesis and as the major source of energy

Answer 22

ATP

Question 23

when ADP is rephosphorylated in the mitochondria by ATP synthase. Coupled to oxidation of hydrogen to water

Answer 23

oxidative phosphorylation

Question 24

interfere with the delivery of hydrogen to the electron transport chain

Answer 24

class A

Question 25

inhibit the transfer of electrons along the electron transport chain to oxygen

Answer 25

class B

Question 26

interfere with oxygen delivery to terminal electron transporter, cytochrome oxidase

Answer 26

class C

Question 27

inhibit the activity of ATP synthase

Answer 27

class D

Question 28

synthesis of ATP may be inhibited in one of four ways

Answer 28

1. direct inhibition of ATP synthase 2. interference with ADP delivery 3. interference with inorganic phosphate delivery 4. deprivation of ATP synthase from its driving force, the controlled influx of protons

Question 29

chemicals causing mitochondrial DNA injury and there by impairing synthesis specific proteins encoded by the mitochondrial genome

Answer 29

class E

Question 30

examples of class A chemicals

Answer 30

fluoroacetate | arsenite

Question 31

examples of class B chemicals

Answer 31

Rotenone | cyanide

Question 32

examples of class C chemicals

Answer 32

CO | alkaloids

Question 33

Example of class D chemical

Answer 33

DDT

Question 34

example of class E chemicals

Answer 34

antiviral (AIDS) drugs

Question 35

sustained elevation of intracellular calcium is harmful because it can result in

Answer 35

1. depletion of energy reserves 2. dysfunction of microfilaments 3. activation of hydrolytic enzymes 4. generation of ROS and RNS

Question 36

what happens during mitochondrial permeability transition

Answer 36

``` abrupt membrane leak proton influx and loss of electrical gradient ATP synthesis stops swelling from influx of water Calcium efflux sudden cell death or necrosis ```

Question 37

programmed cell death

Answer 37

apoptosis

Question 38

four steps of apoptosis

Answer 38

1. release of cytochrome c 2. activation of caspases 3. formation of membrane bound fragments 4. phagocytosis by macrophages

Question 39

apoptosis requires

Answer 39

ATP

Question 40

cysteine proteases that cleave proteins after specific asparate residues. they reside mostly in the cytoplasm in inactive forms with are activated by dimerization or proteolytic cleavage

Answer 40

caspases

Question 41

what decides whether a cell goes through apoptosis or necrosis

Answer 41

the severity of MPT

Question 42

if there is low MPT

Answer 42

lysosomal autophagy of leaking mitochondria

Question 43

if there is intermediate MPT

Answer 43

caspase activation and apoptosis

Question 44

if there is high MPT

Answer 44

cytolysis and necrosis

Question 45

four other mechanisms that lead to cell death

Answer 45

membrane damage by solvents, detergents, venom enzymes lysosomal damage disintegration of cytoskeleton disruption of protein synthesis

Question 46

three ways proteins are repaired

Answer 46

ezymtically to may thiol groups into disulfides with heat shock proteins or chaperones breakdown of protein using ubiquitin

Question 47

how are lipids repaired

Answer 47

repair of fatty acid tails by phospholipases

Question 48

how is DNA repaired

Answer 48

multiple systems

Question 49

is cellular repair ever done

Answer 49

rarely, most cells are replaced | exception is neuronal cells

Question 50

three steps in repair of tissues with germ cells

Answer 50

induction of mitosis dedifferentiation, followed by redifferentiation production of extracellular matrix

Question 51

Three things that can happen when tissue repair fails

Answer 51

tissue necrosis fibrosis carcinogenesis

Question 52

four mechanisms of adaptation

Answer 52

decreasing delivery to target decreasing target density or responsiveness increasing repair mechanisms compensation of dysfunction