Lecture 6 - DA Flashcards
What are xenobiotics?
Artificial organic chemicals made by humans.
How is bioconcentration measured?
Exposure to the chemical (ie. soil or water)
Once at equilibrium, measure the concentration in the organism.
Divide this concentration by the concentration in the environment (ie. soil or water).
What value are bioconcentration factors usually at?
Usually very high, especially for lipid soluble molecules.
What does the fugacity model of chemical absorption attempt to explain?
Biomagnification.
Define fugacity.
Tendency of a chemical to go from one media to another.
ie from food to fish, air to water, water to air etc.
Why do some chemicals bioconcentrate? What does it depend on?
Depends highly on metabolism and excretion.
Define storage detoxification. Name 2 examples.
Removal of a chemical from target organs and blood circulation by locking them in a storage compartment.
Examples include adipose tissue, and bone.
Name 5 sites of action that xenobiotics can act at.
Interaction with an endogenous molecule Sites of metabolism Interaction with enzymes Sites of storage Inert state
Name 3 routes of uptake for terrestrial vertebrates.
Alimentary tract
Skin
Lungs
Name 5 routes of uptake for terrestrial invertebrates.
Alimentary tract Cuticle Body wall Trachea Gills
Name a route of uptake for aquatic mammals and birds.
Alimentary tract
Name 2 routes of uptake for fish.
Alimentary tract
Gills
Name 2 routes of uptake for aquatic invertebrates.
Alimentary tract
Respiratory surfaces
Name 5 sites of storage for xenobiotics. Do they have any effects in this state? What about if the storage unit becomes metabolised later on?
Liver
Lungs
Bone
Kidneys
Membranes
They have no effect if they lack sites of action.
However metabolism of the sotrage unit will lead to rapid release of the toxicant, causing toxicity.
What is the most common storage unit for xenobiotics?
Fat.
Define biotransformation.
Xenobiotic metabolism
How many phases are needed for biotransformation? Name and describe each.
Phase 1 - oxidation, reduction or hydrolysis
Phase 2 - conjugation (ie with glycine)
Where does phase 1 metabolism occur in biotransformation? What about phase 2?
Phase 1 - smooth ER in the liver of vertebrates, hepatopancreas of invertebrates
Phase 2 - cytoplasm or the ER
What does phase 1 of biotransformation usually result in? What about phase 2?
Phase 1 - metabolites with hydroxyl groups
Phase 2 - polar, water soluble product
Does biotransformation always involve all phases?
No, some xenobiotics already have hydroxyls and conjugate directly, skipping phase 1.
Is biotransformation always safe and preferable?
No, sometimes the end metabolite may be more toxic than the parent compound.
What does xenobiotic excretion depend on?
Lipophilicity and hydrophilicity.
How are pollutants taken in by plants?
Atmosphereic pollutants enter through the stomata, though the cuticle may be altered.
Once in the plant, where are pollutants stored? Where are they metabolised?
Spongy parenchyma - storage
Palisade parenchyma - metabolism
If a plant can excrete a pollutant, how does it do so?
Via the epidermis.
What characteristic is important for distribution and persistence of a pollutant in aquatic systems?
Polarity
What do lipophilic compounds associate with in aquatic systems? Name 2.
Sediment and surface oil films.
Pollutants in sediments are more bioavailable to what?
Benthic organisms.
What 2 factors affect sediment bioavailability?
Temperature
pH
Define biomonitoring.
Monitoring the effects of a toxicant that was released into the environment.
What are 3 ways to conduct biomonitoring? Describe each.
- Lab tesing - take samples and do toxicity testing
- In situ biomonitoring - test organism exposed to toxicant in the natural environment
- Ecosystem response - Before and after contamination incident to see effects
Are all filterfeeders good biomonitors?
Yes.
Describe the 4 approaches to in situ biomonitoring.
- Ecosystem changes.
- Measuring concentration of the pollutant in the indicator species.
- Assessing biological effect of the pollutant in individual organisms and relating it to other biotic and abiotic factors.
- Detecting genetic differences that may have evolved in response to a pollutant.
What is the biotic approach to changes in community based on?
Differential sensitivities of species to pollutants.
What is the diversity approach to changes in community based on?
Changes in community diversity.
Describe the ausrivas approach to changes in community. What does it assess?
Assessment in terms of the types of species and relative abundance of families present.
Assesses changes in the system over time.
Should a biomonitor species be very sensitive to the pollutant? Should it accumulate it?
Should accumulate it, but be tolerant to moderate concentrations, not too sensitive.
Should a biomonitor species be active or sedentary?
Relatively sedentary.
What is an ideal lifespan for a biomonitor species? Why?
Months to years, to allow integration of pollution.
What must the bodily concentration of pollutants be unaffected by in the biomonitor species?
They should be unaffected by reproductive cycles or sexual dimorphism.
Should biomonitor species be small or large? Why?
Large to provide adequate biomass for individual analysis.
Define biomarker. What information does it reveal?
A biological response to a pollutant that gives a measurement of exposure or effect.
Allows understanding of the effects of the pollutants on organisms, and how they deal with it.
Name the two types of biomarkers.
Biomarkers of exposure
Biomarkers of effect
Define a biomarker of exposure. What information doesnt it give?
Indicates exposure to a chemical, but no information on the degree of adverse effects.
What would a biomarker of exposure allow the detection and measurement of?
An exogenous substance, its metabolite, or the product of interaction with a target molecule.
Define biomarker of effect.
Measureable biochemical, physiological, or other alterations within the organism that are associated with health impairment or disease.
Name the 3 levels of adverse effects. Give an example for each.
Whole organism – population
-Feminisation of males
Organ – proteins and enzymes
-Metallothionein induction in liver
Cellular and molecular
-DNA damage
What are the 4 kinds of biomarkers?
Physiological
Biochemical
Genetic
Behavioural
Give 4 examples of secondary action of pollutants.
- Poisons disrupting cellular respiration.
- Pollutant presence leading to the release of injurious substances.
- Chelation of metals, leading to a shortage.
- Oestrogenic/androgenic effects, leading to feminisation/masculinisation of the opposite sex.
How do neurotoxins work? Name 2 ways they work by altering membrane integrity.
Disrupts the transmission of nerve impulses.
Can disrupt closure of Na+ channels, or reduce Cl- ion flow.
What is the danger in repairing DNA?
May be repaired, but repaired gene can be modified, leading to oncogene activation.
How can free radical damage to DNA be measured?
The free radical damage occurs to guanine, forming a moiety called fapygua ( ͡° ͜ʖ ͡°).
It is removed from the DNA by acid hydrolysis and analysed by gas chromatography.
What is a DNA adduct?
DNA adducts are structural modifications to DNA resulting from covalent attachment of a chemical or its metabolite.
Sometimes, a parent chemical is less dangerous than its metabolite. How can this be measured?
Highly specific radioimmunoassay or the elisa technique.
DNA damaged by normal wear and tear/ionising radiation is repaired by what mechanism? How What about synthesis?
Repair - incision
Synthesis - replication
DNA damaged by chemical damage is repaired by what mechanism? How What about synthesis?
Repair - excision, resynthesis, and ligation
Synthesis - post translational modification
How can the up/down-regulation of genes in response to pollutants be measured?
cDNA microarrays can be used to assess large numbers of genes at once.
Describe the ALAD pathway in terms of biomarking, and name the pollutant involved. Is it a protective or non-protective response?
ALAD is an enzyme in the haeme biosynthesis pathway.
Inhibition of ALAD specifically relates to lead exposure, inhibition is rapid and long lasting.
Is a non-protective response.
Describe the acetylcholinesterase pathway in terms of biomarking, and name the pollutant involved. Is it a protective or non-protective response?
Breaks down acetylcholine. Inhibition occurs following exposure to organicophosphorus, and pesticides. Is a non-protective response.
Describe the EROD pathway in terms of biomarking, and name the pollutant involved. Is it a protective or non-protective response?
Is a phase 1 biotransformation enzyme. Induction follows exposure to xenobiotics,. Is protective response
Describe the heat stress protein pathway in terms of biomarking, and name the pollutant involved. Is it a protective or non-protective response?
Abundant cellular proteins, protects against heat/stress.
Inducted after various forms of stress, aside from just heat.
Is a protective response.
Describe the vitellogenin pathway in terms of biomarking, and name the pollutant involved. Is it a protective or non-protective response?
Is a yolk precursor protein. Inducted in males after exposure to oestrogenic chemicals. Is a non-protective response.
