Cellular and Tissue Targets of Toxicity

Question 1

Molecular target

Answer 1

somewhere in the body is a biomolecule that the toxicant can effect
-toxicant must be at sufficient concentration at the target

Question 2

toxicodynamics

Answer 2

what happens after the molecular target is altered

Question 3

If a toxicant has high affinity to types of cellular receptors it may:

Answer 3

• directly alter expression of certain genes through receptor complexes
• activate a cell signalling pathway that can lead to altered gene expression

Question 4

reactive oxygen species

Answer 4

cause destruction of target molecules
-distructive oxidative chain reactions of biomolecule with double bond causes lipid peroxidation of membranes, and DNA strand breaks

Question 5

free radical

Answer 5

any atom of molecule that has a single unpaired electron in an outer shell

Question 6

removal of superoxide anion radical

Answer 6

superoxide dismutase, glutathione peroxidase, catalase

Question 7

dysfunction of target molecule

Answer 7

binding to and altering the function of a biomolecule

Question 8

normal cell function

Answer 8

• aerobic respiration to make ATP
• high energy electrons used and transferred to oxygen in a controlled way to form water
• ATP produced is used to drive ion pumps

Question 9

homeostasis

Answer 9

tendency toward a relatively stable equilibrium

Question 10

three critical disorders

Answer 10

ATP depletion, sustained rise in intracellular Ca++, overproduction of ROS and RNS

Question 11

ATP depletion

Answer 11

toxicant that interferes with making of ATP, decreasing ATP in the cell

Question 12

Sustained rise in intracellular Ca++

Answer 12

• increase pumping of Ca++ into the mitochondria, depleting ATP
• disrupt the action cytoskeleton, causing membrane instability
• hydrolytic enzymes activated and start to break down integral membrane proteins and lipids

Question 13

Overproduction of ROS and RNS

Answer 13

• high Ca++ activates the TCA cycle, more electrons flow through the electron transport chain
• ETC gets overwhelmed, electrons mistakenly transferred to oxygen or nitrogen, forming ROS and RNS species

Question 14

Cellular Disfunction

Answer 14

• depletion of ATP deprives ER and plasma membrane Ca++ pumps, elevating Ca++
• compensates by pumping Ca++ into mitochondria, hindering ATP synthase
• Formation of ROS and RNS, inactivating Ca++ pumps
• ROS and RNS drain ATP reserves
• ROS and RNS species directly damage membranes causing leakage of ions out of the cell and Ca++ to leak

Question 15

Necrosis

Answer 15

• cell death
• mitochondrial permeability transition occurs
• ceases ATP production
• plasma becomes permeable
• cell swells and bursts, toxicant can enter other cells

Question 16

mitochondrial permeability transition

Answer 16

pore opens in the mitochondrial membrane and all the contents leak out into the cytosol

Question 17

apoptosis

Answer 17

• programmed cell death, cell kills itself
• triggered by cytochrome c leaking from mitochondria
• associates with caspases and activates them
• caspases signals nucleus to begin apoptosis

Question 18

necrosis vs apoptosis

Answer 18

number and extent of mitochondrial damage

-Necrosis more damage

Question 19

Controlled cell division

Answer 19

• proteins signal cell to begin replication and enter mitosis
• proteins stop cells entering mitosis
• cell super damage, triggered to enter apoptosis

Question 20

oncogenes

Answer 20

• cause cancer

- genes that signal the cell to process through the cell cycle

Question 21

tumor suppressor genes

Answer 21

• genes that signal the cell not to process through the cell cycle
• signal apoptosis or DNA repair when there is irreparable DNA damage

Question 22

mutations become carcinogens by..

Answer 22

• binding to DNA as adducts causing a change in the DNA code

- damaging the DNA backbone or bases

Question 23

toxicants that cause cell death

Answer 23

more cell turnover=more chances of errors in replication=higher probably that genes gain a mutation

Question 24

hormone mimics that signal for a cell to divide when it should not

Answer 24

more divisions=higher probability that a cell will gain a mutation