Mechanisms of Toxicity

Question 1

example of noncovelent binding reaction

Answer 1

small molecule with receptor

Question 2

example of covalent binding reaction

Answer 2

organophosphate (sarin or DFP)

Question 3

example of hydrogen abstraction reaction

Answer 3

oxidation of SH groups

Question 4

example of electron transfer reaction

Answer 4

hemoglobin Fe oxidation=metHB

Question 5

example of enzymatic reaction

Answer 5

ricin hydrolizing rRNA

Question 6

what are the two main effect of targeted cell regulation signalling

Answer 6

1. dysregulation of gene expression

2. dysregulation of ongoing cell function

Question 7

describe what happens with dysregulation of gene expression

Answer 7

• cell division: neoplasia, teratogenesis
• apoptosis: tissue involution, teratogenesis
• protein synthesis: peroxisome proliferation

Question 8

describe what happens with dysregulation of ongoing cell function

Answer 8

• tremor, convulsion, spasm, cardiac arrhythmia

- narcosis, paralysis, paresthesia

Question 9

what are the two main effects of targeted cell maintenance

Answer 9

1. impaired internal maintenance

2. impaired external maintenance

Question 10

describe impaired internal maintenance

Answer 10

The following, when dysregulated, lead to cell injury/death:

1. ATP synthesis
2. Ca2+ regulation
3. protein synthesis
4. micro tubular function
5. membrane function

Question 11

describe impaired external maintenance

Answer 11

dysregulation of hemostasis= bleeding

Question 12

describe what happens when ATP synthesis is disrupted

Answer 12

• oxidative phosphorylation in mitochondria is dysregulated

Question 13

how does impaired internal maintenance lead to necrosis

Answer 13

• mitochondrial permeability transition pore becomes permeable
• H+ stops flowing in, stopping ATP synthesis
• Ca2+ flows out
  energy-dependent processes stop and cell structure eventually fails
• uncontrolled cell swelling, lysis and death

Question 14

how does impaired internal maintenance lead to apoptosis

Answer 14

• release of cytochrome C
• electron transport chain stops
• ATP synthesis stops
• activation of caspases (9 (initiation), then 3 (effector))
• hydrolysis cleavage of specific protein substrate
• controlled cell condensation and release of membrane-bound fragments

Question 15

when does apoptosis happen

Answer 15

• prolongued exposure levels

- early after high exposure levels

Question 16

when does necrosis happen

Answer 16

late after high exposire