biomedical toxicology Flashcards
(146 cards)
1
Q
define toxicant
A
an agent capable of producing a deleterious response in a biological system
2
Q
define organism
A
a thing that has target sites, storage depots and metabolic enzymes
3
Q
what are toxins
A
endogenous agents that interact with proteins, lipids, or nucleic acids in cellular targets
4
Q
what are adverse effects
A
any change from an organism’s normal state
5
Q
what does adverse effects depend on
A
depends on the concentration of an active compound at the target site for a sufficient time
6
Q
define poison
A
a substance that is capable of causing the illness or death of a living organism
7
Q
what toxic substances are termed as poisons
A
toxic substances not directly of biological origin are termed poisons
8
Q
what is venom
A
a toxin recreated by an animal for the purpose of causing harm to another
9
Q
what is mycotoxin
A
a toxin produced by fungi
10
Q
what is exotoxin
A
a toxin secreted by bacteria
11
Q
what is pharmacokinetics
A
examines drug absorption, distribution, metabolism, and excretion within an organism
12
Q
what is pharmacodynamics
A
studies drug interactions with biological receptors
13
Q
difference between drug and toxicant
A
toxicant has no beneficial impact, while drugs have a therapeutic dose
14
Q
what is toxicokinetics
A
the study of kinetics of absorption, distribution, metabolism, and excretion of a xenobiotic under the conditions of toxicity evaluation
15
Q
what is toxicodynamics
A
describes the dynamic interactions of a toxicant with a biological target and its biological effects
16
Q
what was the Bhopal gas tragedy
A
carbine pesticide plant released methyl isocyanate gas
17
Q
what does it mean to have lachrymal properties
A
makes you cry
18
Q
how is toxicity measures
A
toxicity is measured as clinical endpoints which include any disruption to an organisms homeostasis
19
Q
with acute studies, what is the common endpoint
A
with acute studies, a common endpoint is LD50 (lethal dose 50)
20
Q
within chronic studies, what are the common endpoints
A
chronic studies are longer in duration and include endpoints such as reproduction, long-term survival, and growth
21
Q
if the substance that enters circulation is water soluble describe where it goes
A
if it is water soluble, it will stay in circulation
22
Q
if the substance that enters circulation is lipid soluble, describe where it goes
A
if it is lipid soluble, it will cross the cell membrane
23
Q
describe hoe mercury vapour interacts with an organism
A
mercury vapour is readily absorbed into the circulatory system
24
Q
describe the difference between methyl mercury and ethyl mercury
A
- ethyl mercury is much more toxic than metallic mercury
- ethyl mercury is less toxic than methyl mercury
25
describe how MeHg-L0cystein conjugate interacts with an organism
MeHg-L-cystein conjugate is actively transported across the blood brain barrier, which may be responsible for the high Hg levels found in the brain after exposure
26
when exposed to MeHg-L-cystein conjugate, where will it be found
after exposure, high concentrations will be found in the brain, as it is actively transported across the blood brain barrier
27
describe the interaction and correlation between MeHg and extracellular glutamate
MeHg stimulates extracellular glutamate levels and the over activation of glutamate receptors increases Ca2+ influx into neutrons, therefore leading to the activation of important pathways involved with cell death
28
what are the six steps in the systematic overview of a toxicant
1. exposure
2. absorbed
3. delivered (to target site)
4. bioactivated
5. detoxified
6. excreted
29
three attributes of target
- reactivity
- accessibility
- critical function
30
which are more reactive- proteins or dna
proteins are more reactive than stable dna
31
describe non covalent binding reactions with target molecules
- reversible
- lock/key inhibitors
- membrane receptors
- enzymes
32
example of non covalent binding with target molecules
dna intercalates (insert within the stacked bases)
33
describe covalent bonding reactions with target molecules
- irriversible
- permanently alters target
- react with nucleophilic enters in dna and proteins
34
example of covalent binding with target molecules
- electrophilic epoxides
| - carbon monoxide
35
describe the effect of dysfunction of a target molecule
alteration of target configuration
| -tertiary protein structure or dna template
36
describe the effect of destruction of a target molecule
- crosslinking of proteins and nucleic acids
| - covalent binding of toxicant with targets that are released from cells can sometimes evoke an immune response
37
what is the toxoconetic process
```
xenobiotic
absorption (external membrane barriers)
distribution (blood plasma to tissues)
metabolism (phase 1 (CP450, 2(increased polarity)
excretion (kidneys' etc)
```
38
four routes of absorption are
inhalation
direct contact
ingestion
injection
39
two ways of crossing the biological membrane
- passive diffusion
| - active transport
40
characteristics favouring absorption with inhalation
- large surface area
- large blood supply
- phagocytosis and migration
41
toxicity through the pulmonary route depends on?
- particulate size and volatility
- ability to diffuse
- affinity for transporters
42
what chemical has a very active transport through the skin
DMSO
43
how to increase skin absorption
- hydration
- solvent effects
- temperature
- amount of dermal appendages
44
how does hydration increase dermal absorption
proves an aqueous media and causes cell swelling
45
how do solvent effects increase dermal absorption
can alter lipids in the membrane
46
how does temperature increase dermal absorption
increasing temp increases blood flow
47
characters favouring absorption within the gastrointestinal tract
- single cell lipodial membrane
- large surface area
- high blood and lymph flow
- variable ph
- many specialized transport proteins
48
describe passive uptake
passive uptake is the most common way that xenobiotics cross cell membranes and does not require the input of energy
49
what are the three factors that determine the rate of passive transfer
- differences in concentration
- polarity
- size
50
explain how differences in concentration will determine rare of passive transfer
differences in concentration of the substance on opposite sides of the membrane
-substances move from
51
example of a lachrymal agent
methyl isocyanate
52
what is a lachrymal agent's property
makes u cry
53
what is the most abundant target molecule in the human body
proteins
54
what types of reactions can occur with target molecules?
- non covalent
- covalent
- fragmentation
- crosslinking
55
what are the four aspects of toxokinetics
absorption, distribution, metabolism, and elimination
56
which route of absorption probably results in the least toxicity
dermal (skin)
57
which route of absorption results in the greatest toxicity
inhalation
58
which factor does not influence rate of distribution
- blood flow
- physiochemical properties
- protein binding
- passive diffusion or active transport
- none of the above
none of the above
59
what factors influence rate of distribution
- blood flow
- physiochemical properties of the chemical
- protein binding
- passive diffusion or active transport
60
what are the three barriers to distribution within the body
- blood brain barrier
- blood placenta
- bood testis
61
what is blood testis
type of cell barrier
62
how does methyl mercury pass through blood brain barrier
by reacting with cytosine and utilizing the methionine transporter
63
what are the two major routes of excretion
kidney (urine), and liver (bile)
64
phase 2 metabolites are generally excreted well through what
phase 2 metabolites are generally excreted well through the bile
65
epinephrine acts as a
- agonist
- antagonist
- hormone
- suicide substrate
epinephrine acts as a hormone
66
endocrine disruptors can not interfere with hormone:
- production
- transport
- metabolism
- elimination
- synthesis
endocrine disruptors can not interfere with hormone synthesis
67
which of the following can not act as an anti-estrogen
- THC
- DDT
- PCB
- estradiol
estradiol acts as an anti-estrogen agent
68
How many pounds of BPA is used/year in consumer products
6 billion pounds of BPA are used each year
69
what are the possible edicts of BPA
- increase prostate weight
- decline in testosterone
- changes to genital tract
70
what does TCDD cause
chloracne
oxidative stress
endocrine disruption
cancer by compounds activated by cyp450
71
why does 50% occupancy of Hb by CO result in death, while 50% occupancy due to low oxygen does not?
Co interferes with oxygen unloading by increasing the Hb affinity for oxygen
72
why is the lethal dose of HCN lower than potassium cyanide
HCN is a neutral compound with greater membrane permeability
73
how many over-the-counter products contain Tylenol
600
74
how many people die in the US/year from Tylenol
500
75
what is Tylenol toxicity caused by
bioactivation into NAPQI that reacts covalently with liver proteins
76
why is it not a good idea to mix Tylenol and alcohol
- alcohol depletes GSH
| - Alcohol can induce CYP450 to cause Tylenol bioactivation
77
what diseases are a result of protein oxidation
- diabetes
- muscular dystrophy
- alzheimers
78
what structural change causes the B-form DNA duplex to produce the A-form duplex
change in deoxyribose "sugar pucker "
79
what is the final step in chemical carcinogenesis
metastasis
80
what are the steps, in order of chemical carcinogenesis
initiation
bioactivation
proliferation
metastasis
81
how many compounds are establishes carcinogens
100s
82
PAHs are historically thought to cause:
scrotal cancer (like the boys from marry Poppins)
83
which region of PAHs is most reactive towards electrophiles
K-region
84
the activated compound thought to produce DNA adducts by BP is called
BPDE
85
why is a simple arena oxide unreactive towards DNA
it undergoes rapid isomerization into a stable phenol, making it unable to react
86
Where are aromatic amines present
- tobacco smoke
- exhaust
- organic dyes
87
where are aromatic amines NOT present
pesticides
88
The dna reactive intermediate for an aromatic amine is called
nitrenium ion
89
what do polycyclic planar structures cause
cancer
90
which N-linked c8-aryl-dG adduct lacks mutagenicity
An-dG
91
describe AAF-dG on mutagenic outcome
highly mutagenic
92
describe AF-dG on mutagenic outcome
highly mutagenic
93
describe ABP-dG on mutagenicity
weakly mutagenic
94
describe An-dG on mutagenicity
lacks mutagenicity
95
what is the major oxidative DNA base lesion called
8oxoG
96
06-methylguanine DNA methyltranferase is an example of?
- glycosylase
- BER enzyme
- direct reversal repair enzyme
- NER enzyme
06-methylguanine DNA methyltransferase is an example of a direct reversal repair enzyme
97
Why is BER (base excision repair) convergent
it is a family of repair enzymes where they all produce the same abasic site
98
why is NER (nucleotide excision repair) highly promiscuous
because it removes a wide range of DNA damage
99
what is the first enzyme employed in NER
DNA exonuclease
100
what diseases are a result of defective dna repair
- ataxia telangiectasia
- blooms syndrom
- xerderma pigmentosum
101
what are the products of acetylcholine hydrolysis by cholinesterases
choline and acetic acid
102
what is the purpose of acetylcholine hydrolysis by cholinesterase's
it permits the termination of impulse
103
how many amino acids are in the 3-finger protein "fasciculin" within venom
61
104
what is the mechanism of action of fasciculin
blocks acetylcholine binding to acetylcholinesterase
105
how many amino acid residues are in cobra toxin
71
106
the mechanism of action for cobra toxin:
blocks aceytlcholine binding to its receptor
107
what is venom milking used for
antibodies against the toxin within the venom
108
of nerve agents, which one I the least volatile
- sarin
- soman
- tabum
- VX
VX is the least volatile
109
of nerve agents, which one has the lowest LD50 from dermal exposure
VX
110
of nerve agents, which one has the shortest aging time
soman
111
what is the mechanism of action for man-made nerve agents
blocks acetylcholine from undergoing hydrolysis by the esterase
112
what are the routes of failed excretion
1-lipid soluble: bioaccumulation
2- reabsorbed kidney or GIT
3-binding:bioaccumulate (ie lead)
113
T or F
| metabolism only reduces toxicity of chemicals
false- it can increase or decrease toxicity
114
what is an agonist
mimics a hormone in binding productively to a receptor
115
what is an antagonist
mimics a hormone in binding non-pruductively
116
what do endocrine disruptors do
mimics naturally occurring hormones by blocking the way natural hormone and their receptors are made or controlled
117
what are the three mechanisms of endocrine disruptors
1-binding and activating the estrogen receptor (acting like an estrogen)
2-exogenous estrogens can bind to the estrogen receptor but the affinity is usually only a fraction of the binding affinity of estradiol
3- binding but not activating the estrogen receptor (acting an an anti-estrogen
118
describe BPA estrogenicity
BPA. closely mimics the structure and function of hormone estradiol with the ability to bind to and activate the same estrogen receptor as the natural hormone
119
when is Bisphenol s (BPS) used
used where the legal prohibition on BPA allows products containing BPS to be labelled BPA free - although it also had endocrine disrupting properties
120
what is TCCD
tetrachlorodibenzo-p-dioxin
| -is a contaminant in the herbicide Agent Orange and was shown to produce birth defects in rodents
121
what are the mechanisms of action for dioxins
- dioxins are taken up through the cell membrane passively
- recognized to be receptor-mediated toxicants
- exerts effects through interactions with a specific intracellular protein (aHr)
- functions as a hormone- initiating a cascade of events that is dependent upon the environment of each cell
122
what is AhR
its a liugans-activated nuclear transcription factor
123
what does AhR do
mediated xenobiotic signalling to enhance the expression of target genes, including p450s
124
what happens when TCDD binds to AhR
the complex interacts with genes that promote RNA polymerase to make mRNA to facilitate protein production
125
what are the adverse effects of TCDD
-chloracne- an inflammatory condition
-promotion of cancer by other activated compounds
-oxidative stress m
=endocrine disruption
126
how much hemoglobin does a heathy human have
15g/L
127
what does cyanice do
blocks the use of oxygen
128
how does cyanide block the use of oxygen
-binds to cytochrome oxidase and inhibits the last step of the ETC
-then no ATP can be created
= respiratory arrest and death
129
what accounts for 95% of acetaminophen metabolism
glucuronidation and salvation
130
what is acetaldehyde
reactive electrophile that reacts directly with GSH
131
grapefruit juice inhibits p450 which would do what
decrease the production of NADPQIU
132
how much of protein in an 80 year old human is oxidized
20-50%
133
what are tutor suppressors
normally function to prevent cell growth/ division
134
what are oncogenes
normally promote cell growth
135
what are the steps in chemical carcinogenesis
1- biotransformation
- initiation
- fixation
- gene expression
- growth/poliferation
- progression
- metastasis
136
what is B-epigenestics
increase the likelihood of tumour development
137
what do PAHs need to show toxicity
bioactivation by p450
138
what is the most abundant carcinogen in car exhaust
benzo[a]pyrene
139
T or F
| mutated DNA is damaged
false- its just different
140
describe direct reversal mechanisms
altered dna bases chemically covered back to the standard structures w/o the removal from the DH
141
describe base excision repair
bases are attached to backbone - and are removed by hydrolysis of the glycosidic bond
-convergent and specific
142
describe nucleotide excision repair
recognize and remove the damaged portion of a dna strand
| -highly promiscuous
143
what is global genome repair
mechanism for dealing with stalled replication forks
144
what is transcription couples repair
mechanism for dealing with stalled transcription complexes
145
what does global genome repair protect genome against
against mutations and ensures that cell replication can be completed
146
what does transition couples repair protect
protects actively transcribed genes where lesions on the transcribed strands would become traffic jams
