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FLC 613 – Biology of Toxins
Study Questions
Second Lecture (8/28)
1. Grab your dictionary (or go to www.merriam-webster.com/) and look up the definition of
"toxic" and “toxin”. Sorry, but the definitions found at www.urbandictionary.com, while
technically correct, are not acceptable as answers to this question.
2. What are the signs of water intoxication? What is the direct physiological cause of water
intoxication?
3. How does ecstasy exert its effects in the brain? What are the three parts of the brain
involved in this?
4. Why is ecstasy termed the “Hug Drug”? How does ecstasy bring about this effect?
5. What other drug is ecstasy chemically very similar to? How do the effects of Ecstasy in
the brain differ?
6. What are two adverse effects that ecstasy causes in neurons?
7. Why do people tend to drink lots of water after taking ecstasy at a rave?
8. Is Ecstasy addictive? Give me three lines of evidence relating to this.
9. Why do ecstasy users tend to drink lots of water at a rave?
10. What is water intoxication? Use a flow chart to facilitate a discussion of how water
intoxication develops following ecstasy use.
11. What is meant by the term cerebral edema? What are some symptoms of cerebral
edema? Why is cerebral edema potentially so dangerous?
12. What are the two ways that ecstasy use during a rave can lead to death? Why is brain
herniation fatal? What are some potentially fatal consequences of excess hyperthermia
(heat stroke)?
Third Lecture (9/2)
13. Is oxygen be toxic? What are some of the symptoms of oxygen toxicity?
14. Is carbon monoxide always toxic? What’s a neurotransmitter?
15. Are there any substances that aren't toxic? What determines whether something is toxic?
16. Why do organisms produce toxins?
17. What is meant by the term “venom”?
18. In the case of male lions, when I said that male lions are under sexual selection, what
exactly did I mean? When I said they are also subject to natural selection, what evidence
did I site?
19. In the case of male lions, did natural selection work in the same ‘direction’ ( = tending to
cause the same response) as sexual selection, or in the opposite direction?
20. Repeat Questions #9 and #10 for human males. We discussed two ‘processes’ that
appear to be examples of natural selection on human body size. What were those two
processes and how would they tend to keep male body size in check?
21. What explanation might biologists propose to account for the fact that human females
aren’t much larger than they are?
22. The take-home message of our discussion of natural & sexual selection, and the
evolutionary responses they can cause, was…?
Fourth Lecture (9/4)
23. What do each of the letters in the acronym ADAME stand for?
24. With respect to toxins, what is meant by the term “absorption”? By the term
“distribution”?
25. Describe the routes of absorption of a toxin. Which route is most frequently used by
toxin-producing organisms? Why is that? Which one is probably the most difficult way
for a toxin to enter the body? Which is probably the easiest, and why isn’t it more
commonly used?
26. What organism uses lungs as the route of administration for its toxin? How would that
toxin benefit the organism producing it?
27. What organ system generally plays the key role in distribution of toxins? Present a
diagram of that system and use that to describe in general terms the flow of blood
throughout the body.
28. Which organ gets a disproportionately large share of the blood pumped by the heart?
Why is it important that this happen?
29. Essentially all of the blood that doesn’t flow to the head and upper body flows through
the __________________ on its way back to the heart.
30. We discussed several routes be which a toxin can enter an organism: lungs, IV, IP, IM,
GI, skin. From the perspective of an organism producing a toxin, discuss the relative
strengths/drawbacks of each route. (Hint: you’ll want to include distribution pathways
and sites of detoxification in your discussion.)
31. Present a block diagram of a human’s body fluid compartments, along with some rough
statement about their respective relative volumes (you can use terms like “biggest”,
“smallest”, “lots”, “little”, etc.).
32. Discuss the properties of the barriers that separate the various body fluid compartments,
and speculate about the implications of the barrier’s properties for organisms ‘trying’ to
develop toxins that target specific tissues.
33. What is the primary function of your kidney, and which body fluid compartment does it
work on?
Fifth Lecture (9/11)
34. For a toxicologist, what is meant by the term “action”? By the term “response”? How do
the two terms relate to one another? Is death the only useful measure of an organism’s
response to some toxin? Give an example of a plant toxin that produces a subtle, but
potentially serious, response.
35. What are the three factors that determine the action of a particular toxin?
36. What is meant by the term “dose”? In what units are dosages are usually measured?
37. Why do toxicologists usually administer a mass-specific dose of a substance they’re
testing for its toxic properties?
38. What are the three factors that determine the effective dose of a particular toxin?
39. Why are lipophilic toxins often more toxic than more polar, hydrophilic toxins?
40. What are some potential problems for an organism that ‘wants’ its toxin to attack
intracellular targets?
41. As far as a toxin is concerned, what are some benefits to being non-polar (lipophilic)?
What are some drawbacks to being polar?
42. Graph the following data and estimate the LD50 for the two toxins:
% of Individuals Showing Response
Dose
( mg/kg )
0
10
20
Toxin 1
0
0
2
Toxin 2
0
0
0
30
40
50
60
70
80
18
56
83
94
97
99
3
96
100
100
100
100
43. In the preceding question, what would you call the NOAEL for Toxin 1? For Toxin 2?
44. With regard to the toxins used in the preceding question, which toxin would be considered
to be more toxic? Justify your answer.
45. What’s the difference between LD50 and ED50?
Sixth Lecture (9/16)
46. Suppose you’re a toxicologist working for a pharmaceutical firm, and have been charged
with determining whether a newly-discovered chemical would be a good candidate for
use in the treatment of brain cancer. What data would you want in order to make this
assessment, and what experiment(s) would you perform to gather those data? Now, using
an appropriate graph to facilitate your discussion, describe how you would come to a
conclusion about the chemical’s suitability.
47. What is your opinion of having to incorporate a drug’s cost into the decision about
whether to prescribe it for a patient? If you think it’s a problem, can you propose any
solution(s)?
48. Draw survivorship curves for renal and breast cancer, with and without Avastin
augmentation therapy. Use your graphs to facilitate your responses to the following
questions:
a. What is meant by the statement “Avastin increased median survival time by 2-4
months”?
b. In your opinion, is median survival time the best measure of what a survivorship
curve tells us?
c. In your opinion, is median survival time the best measure of a drug’s effect on
survivorship?
d. For which type of cancer is Avastin more effective, renal or breast? Justify your
answer.
49. Construct a graph that clearly illustrates the presence of susceptible and resistant
individuals in a population. Use the graph to discuss how resistance to an antibiotic (or a
toxin) can evolve.
50. Describe the two major mechanisms of antibiotic function, and the three major ways that
bacteria are able to resist the effects of antibiotics.
51. Describe an experiment that suggests an explanation for why all bacteria aren’t resistant
to antibiotics.
Seventh Lecture (9/18)
52. Give me two examples that provide evidence that toxins are costly for the organisms than
produce them.
53. Why do the elderly and very young tend to be more susceptible to many toxins?
54. There’s usually considerable intraspecific ( = within a species = among the individuals of
a species) variation in susceptibility to most toxins. Can you suggest any explanations
for this variation in susceptibility?
55. What is meant by teratogenic?
56. How does thalidomide produce its effects? Are there any differences in how thalidomide
affects various kinds of mammals?
57. What take-home message(s) do you draw from the comparative data I gave you about the
effects of thalidomide in humans and other mammals?
58. What does the term metabolism mean with respect to toxins?
59. What is a xenobiotic?
60. What is the primary objective of the body’s metabolic ‘attack’ on toxins, and how is this
objective achieved?
61. Define and discuss biotransformation, and suggest reasons for why it occurs in two
distinct phases. Where in the body does most biotransformation occur?
62. What is cytochrome P450, what does it do, and why is it important to toxicology? Why
do use the term “cytochrome”?
63. Which phase of biotransformation involves P450?
64. Why are there so many different P450 types (families & subfamilies)?
65. How does the term inducible relate to cytochrome P450?
66. Why is it a good idea for P450s to be inducible?
Eighth Lecture (9/23)
67. What is the phylogenetic distribution of P450? That is, in what kinds of organisms is
P450 found?
68. What do biologists believe to have been the original function of P450?
69. Which CYP subfamily is the most abundant in humans, and where is it found? Which
CYP subfamily seems to be dominant in terms of biotransforming the widest range of
xenobiotics? Give some examples of the drugs (medicines) that this CYP subfamily
metabolized.
70. Why do physicians, especially anesthesiologists, want to know about what medicines you
are taking? Do you think they should they care about so-called “natural remedies”?
71. How do histamines affect the activity of their target cells? Give me four examples of
processes that are regulated by histamines, and describe the effect of histamine in each
case..
72. How do antihistamines work? What are the desirable and less-desirable side-effects of
most antihistamines?
73. Tell me about CYP3A4 and nonsedating antihistamines. What is the general lesson to be
derived from this story? Define bioactivation, and give an example.
74. Which CYP family is the most diverse in humans? What are some xenobiotics that it’s
involved in biotransforming? What role does it play in metabolism of alcohol? What is
an important adverse consequence of this?
75. Why do physicians, especially anesthesiologists, want to know about your alcohol
consumption?
76. What is meant by the term genetic polymorphism, and how does it relate to P450s and
medical practice?
77. Summarize the three ways that drug interactions can occur.
78. Offer an explanation for the results of the erythromycin hazard paper you read.
79. Describe and discuss Phase II biotransformation of xenobiotics. What are glucuronic
acid and glutathione?
80. What organs are mostly responsible for Phase II biotransformation reactions?
81. Discuss why biotransformation involves two distinct phases. In other words, tell me
about the relative costs and benefits of the Phase I and Phase II reactions.
82. Using Tylenol as an example, discuss bioactivation. Do symptoms of liver damage show
up immediately? Why or why not? Would the problem be worse in chronic alcoholics?
Justify your answer.
83. How is it possible that most Tylenol overdoses are inadvertent?
84. What is a significant problem associated with CYP2E1, the P450 that has primary
responsibility for ethanol biotransformation? How did liver cancer rates in male and
female humans compare?
85. By what avenue are most toxins excreted? What are some benefits and drawbacks to this
avenue?
86. Describe the excretion of toxins in the bile. Give me one benefit and one drawback to
excreting toxins via the bile.
87. Why is bile green?
88. What is the cause of “milk sickness”? Offer an explanation for why the toxin is usually
found only in plants that experience a summer drought period (hint: think back to our
discussion of wild ginger and banana slugs.).
89. What do biologists mean by the term “gene expression”?
90. What does DNA polymerase do, and why is it important?
91. Give a brief description of the events involved transcription and translation. What enzyme
plays a key role it the process? What do the ribosomes do?
92. What is the importance of the amino acid sequence of a protein?
93. Which type of molecule – polar or non-polar – moves through a membrane more readily?
Why is this?
94. What are some functions that plasma membrane proteins perform?
95. Compare and contrast a cell surface receptor with an enzyme. Why are these receptors
important?
96. Using an appropriate diagram (that you produce), discuss signal transduction in cells.
97. What is the “cytoskeleton”, and why is it important to cells? What can happen if the
cytoskeleton is disrupted?
98. What is phospholipase A2, and what does it do for us? How have venomous snakes
adapted the basic molecular structure of PLA2 to make it toxic? Give me 4 different cell
types that are specifically targeted by different snake phospholipases.
99. What are hemolysins and leukocidins, and how do they work?
100. What is the Red Queen Hypothesis, and how is it relevant to the biology of toxins?
101. With respect to the California squirrel-rattlesnake story, suggest a possible explanation for
how some squirrel populations are able to be resistant to the snake’s venom.
102. Below is a map showing the NM distribution of a hypothetical small rodent (the black
area) and a hypothetical venomous snake that preys on it (the red stippled area). The dark
red area shows the zone of overlap of the two species’ distributions, which is the only
region in NM where the snake species actually preys on the rodent.
103.
104.
105.
106.
107.
108.
109.
110.
111.
112.
113.
114.
Your mission, should you choose to accept – which I know you will – is to design a
research project that would test whether coevolution of the snake and prey has occurred.
So, design the project, tell me what kind of data you’d collect, where you’d sample, etc.
Are there any other data – besides the map of the snakes’ and squirrels’ ranges – you’d
like to have in order to better test the hypothesis of coevolution of predator and prey in
this system? HINT: what else did we know about the California rattlesnake & squirrel
populations that helped us demonstrate coevolution?
Use a simplified version of cell metabolism & energy production as a basis for a
discussion of how hypoglycin and cyanogenic compounds exert their toxic effect.
Where does taxol come from, how does it work, and why is it used to treat certain kinds
of cancer?
What is the organism that produces amatoxins, and what is the mechanism ‘used’ by each
toxin?
What is phagocytosis? What are macrophages, and why is phagocytosis important to
them? What do macrophages do for us?
What are the commonalities in the way Salmonella typhi and Shigella dysenteriae attack
their target cells? What are their primary target cells? Why do S. typhi and S.
dysenteriae ‘want’ to remain inside their target cells? What is different about S.
dysenteriae once it gains entry to the cell’s cytoplasm?
Describe the A-B mechanism of toxin attack on a target cell. Why is it necessary? Give
me two bacteria that use this mechanism to attack their target cells.
What is meant by the term “biofilm”? How do bacteria produce a biofilm?
We discussed two species of bacteria that produce biofilms – Corynebacterium
diphtheriae and one other. What is that other bacterium? How do these two species of
bacteria actually cause death of cells that they ‘attack’?
Why was diphtheria known as the “White Strangler” and “Strangling Angel of
Children”?
How do bacteria benefit from the ability to produce biofilms?
What did I say was so disgusting about Pseudomonas aeruginosa? (hint: think pus.)
What mechanism is employed by ricin and abrin? Do they use an AB mechanism to get
the toxic property into target cells? Can you think of any possible explanation(s) for why
abrin is 75x more toxic that ricin?
115. Propose an explanation (or explanations) for why chickens are so much more resistant ( =
less susceptible) to ricin than are mice.
116. What is MAPK, and why is it important to cells?
117. What are oncogenes?
118. Using a suitable diagram, present a detailed discussion of how the G-protein signaling
pathway functions.
119. Why do we say that the G-protein signaling pathway functions like an ON-OFF switch?
What is a benefit of having a signaling pathway that works in this fashion?
120. What is adenyl cyclase, and what does it do?
121. Where and how does pertussis toxin work? What is the main symptom exhibited by a
person who’s infected by the bacterium that produces pertussis toxin? Why would the
bacterium want its victim to exhibit this symptom?
122. What is the other toxin produced by Bordetella pertussis? What does that toxin do, and
why does B. pertussis need to produce it?
123. Discuss the three components of anthrax toxin, tell me what each does, and tell me why
the anthrax bacterium would want the three components to do what they do.
124. Present a simplified diagram of your gastrointestinal ( = digestive) system, and briefly
describe the function(s) of:
• the stomach.
• the small intestine.
• the large intestine.
• the gall bladder.
• the pancreas.
• the gastroesophageal sphincter.
• the pyloric sphincter.
125. What is the primary stimulus for the vomit reflex? For the gag reflex? What is their
function?
126. Give me six toxins that primarily target the cells lining the small intestine, their source,
mechanism of action, and the effects they cause. (note: terms such as “rotten meat”,
“uncooked chicken”, “impure water”, etc. DO NOT count as sources. I want organism
names!) Why do these organisms want to cause the symptoms their toxins produce?
127. Do you think a toxin such as ricin would cause vomiting and/or diarrhea? Justify your
answer.
128. Tell me about the Ordeal toxin plant (the Calabar bean, Physostigma venenosum., and is
use in the pre-colonization Nigerian judicial system.
129. Using a suitable flow chart (block diagram), discuss information flow through the
nervous system.
130. Diagram and label a typical neuron.
131. What is an action potential? Why is the ability to generate action potentials important?
What do organisms use action potentials for?
132. Use a flow chart as a basis for a discussion of the ion-channel events responsible for the
action potential.
133. How do action potentials spread from point to point along a neuron?
134. List four toxins that target gated sodium channels, and give their source, their effect on
the sodium channel, and the type of symptoms they cause.
135. Diagram a synapse and use this diagram as the basis for a discussion of transmission of
action potentials across a synapse. Be sure to include the following terms in your
discussion:
136.
137.
138.
139.
140.
141.
142.
• Synaptic bulb
• Synaptic vesicle
• Neurotransmitter
• SNARE complex
• Exocytosis
• Postsynaptic receptor
• Degrading enzyme
• Gated ion channels
What determines whether a given neuron, neurotransmitter, or synapse is excitatory or
inhibitory? (that’s kind of a toughie, but the knowledge very important, so be sure you
understand the answer)
Which type of neuron – excitatory or inhibitory – is more important in the brain and
spinal cord. Justify your answer with data I presented in lecture.
We discussed five toxins that specifically target excitatory ACh-mediated synapses of
neurons that the brain uses to cause our muscles to contract. List the five toxins, along
with their source, mechanism of action, and symptoms they cause.
Describe the anatomy & function of the various parts of the nervous system, including
the following parts of the brain:
Frontal cortex
Visual cortex
Hippocampus
Limbic system
Hypothalamus
Medulla
What is prosopagnosia?
What is object agnosia?
What is the take-home message that you derived from our discussion of object agnosia
and prosopagnosia?