REFRESHER QUIZZES 10-17

Explain why cadmium accumulates in rice grains. When we eat cadmium-containing rice, where does cadmium preferentially accumulate in our body?

Cadmium accumulates in rice grains because cadmium mimics the essential nutrients in rice. Cadmium can be taken up by rice through bypassing solubility barrier, translocation barrier and phytotoxicity barrier, then accumulates in the grain. Although only less than 5% of cadmium can be absorbed through food (oral), it is preferentially accumulated in kidney liver and bone..

Describe the protective mechanisms of metallothionen (MT) against toxic heavy metals, like cadmium.

Metallothionein is a protein which 30% of its amino acids as cysteine (-SH), which is also an antioxidant. When toxic metals come into contact with Zinc, it allows for the metal to be easily binded kicking Zinc out. (Metallothionein (MT) has three protective mechanisms. When heavy metals are present, they displace zinc (Zn) and bind to MT instead. This protects the cell in three ways: MT sequesters toxic metals to reduce their cellular toxicity, the released Zn activates Zn-dependent transcription factors to increase MT production, and the thiol (-SH) groups in MT provide antioxidant activity that helps neutralize reactive oxygen species (ROS), such as those generated by cadmium.) This alerts the mechanisms to contain the toxic metals instead of being distributed.

Explain how lead (Pb) in the environment kills eagles and California condor.

Lead in the environment is affecting the eagles and the California condor through litter, DDT, poaching, and the destruction of their natural habitats. For example, wildlife hunting would use lead bullets, and if an animal was killed with a lead bullet, leftover fragments stay withing he animal's corpse. This causes other predator animals to end up consuming the lead, possibly having them die from lead poisoning (biomagnification). Since Pb is a neurotoxin virtually affecting all neurons, Pb-poisoned eagles end up with losing vision and impairment of motor activity (fly, swallowing food, etc), leading to death by starvation.

Define the possible toxic mechanisms by which lead (Pb) causes neuronal dysfunction and memory impairment.

The possible toxic mechanisms by which lead causes neuronal dysfunction and memory impairment. Pb can substitute for calcium and dysregulate calcium homeostasis and signaling in the brain. Calcium activates important signaling molecules to strengthen synapse connectivity and conductivity, as well as synaptogenesis. When lead is present, it inhibits the release of neurotransmitters (the Ca2+ signaling), which impairs or weakens synapses. This can lower IQ or affect memory. 

Describe the primary route of absorption and target organ(s) of 1) methylmercury (MeHg) and 2) vapor mercury. Describe the toxic mechanisms of action of MeHg and vapor Hg in these organs, and describe a major metabolism of MeHg and Hg to be excreterd from the body.

The primary route of absorption and target organ of methylmercury and vapor mercury is through forming strong complexes with thiol-containing molecules. This targets the kidney and the brain, however, methylmercury is a charged molecule making it hydrophilic which does not allow it to cross the blood brain barrier so in order to bypass, it mimics methionine by forming a strong complex with thiol-containing molecules. For vapor mercury t undergoes a conversion where Me is removed in the nervous system, once this conversion is complete it can no longer exit out of the brain due to the positive charge which then leaves Hg2+ to linger, explaining the large half-life.

The process of metabolism and excretion of MeHG and Hg starts with it being trapped and accumulated within the brain and kidney, it then goes through a biotransformation within the liver to go through the excretion process. This is where Hg2+ -GSH conjugation to excrete Hg in the urine and feces. 

Describe how Hg released from mining and coal plants eventually reaches out to pumas, mountain lions and other wild animals living in the coastal area in SF and Santa Cruz.

Mercury Reached the wild animals living in the coastal area through bioaccumulation. Mercury from burning coal was combining with bacteria from the sea, transforming it into methylmercury. This causes the fog to form over the ocean, lifting the methylmercury and depositing it on land, where deer consume it through lichen. The deer’s predators, such as cougars, pumas, and mountain lions, would eat the deer, causing methylmercury to bioaccumulate within their systems.

Describe the difference in generation of primary and secondary particulate matter (PM). 

The generation of primary particulate matter (PM) and secondary PM is how they're generated. Primary PM is PM that is directly generated and released from the source such as traffic and burning fossil fuels. Secondary PM is not directly emitted but is formed via chemical reactions from other sources within the atmosphere. 

Describe the proposed toxic mechanism of particulate matter (PM) leading to atherosclerosis.

The toxic mechanism of PM leading to atherosclerosis begins when PM damages the inner layer of the endothelial cells, to which immune cells are recruited to repair the tissue damage. This repeated damage causes slow accumulation of plaque thickening and stiffening of the artery, affecting the blood flow. This can then increase the risk of strokes and heart attaack 

Explain the mechanism of silicosis in the lung by inhaling fine silica particles or asbestos.

The mechanism of silicosis begins when very fine silica dust enters the alveolar sac, affecting the macrophage that tries to degrade the silica dust. Being unable to break it down it begins to damage the tissue with reactive oxygen species (ROS) in the surrounding tissue. This signals for more inflammatory cells to invade, and as more cells die, collagen and elastin deposition increase. Macrophage not being able to digest silica because of the mineral so once it dies, silica will decrease to the alveoli sac repeating the cycle. Silica particles and asbestos cannot be degraded. 

Explain the mechanisms by which inhalation exposure to radon gas causes lung cancer.

Inhalation exposure to radon gas causes lung cancer through the emission of alpha and beta particles entering the lung, which damages cell membrane, enzymes and organelles directly or indirectly. Indirectly involves the alpha particle attracting electrons away from nearby molecules and cause the molecules ot become ions. Ionizing radiation hits water to generate ROS, the ROS can then form DNA adducts or cause DNA strand crosslinking. Together, these types of damage can lead to DNA mutations and ultimately tumorigenesis in lung epithelial cells.

Describe the toxic mechanism of action of vinyl chloride leading to DNA mutation and tumorigenesis.

The toxic mechanism of vinyl chloride begins through being metabolized in the liver by CYP2E1 to form the reactive species of Chloroethylene oxide. This then binds to DNA bases to form different types of DNA adduct formations with the most prevalent being 7-(2-oxoethyl)- guanine. These adducts then form mutations in the DNA, causing base-pair substitutions. The accumulation of these DNA mutations leads to tumorigenesis, causing tumor formation in the liver. 

What is the major source for microplastic contamination in the environment, and how do they travel far from the origin and possibly accumulate in arctic glacier and European Alps?

The major source for microplastic contamination in the environment stems from rubber tires, synthetic fabrics, polymer paints, and consumer products from around the world disintegrating into small particles. These deposits reach the sea where waves and UV radiation turn them into tiny microplastic fragments by breaking them down. Afterwards, winds and thermal currents carry the microplastics into the atmosphere causing the deposits to be carried through the air. They accumulate in the Arctic and Alps through clouds and snow, trapping them in and having them land on the ice and sea surface.

Explain, from the chemistry point of view, why PFAS are so stable in the environment.

PFAS are so stable in the environment because of their chemical properties involving carbon-fluorine (C-F Bond), which is one of the shortest and strongest covalent bonds, electronegativity, and has no polarity. It is highly resistant to breakdown in the environment due to its carbon structure being similar to a fatty acid.

Describe the toxic mechanism of action of trichloroethylene (TCE) leading to tumor formation.

The toxic mechanism of action of trichlorethylene involves TCE binding to P450 to make TCE oxide. Due to TCE being a double bond it is more prone to react to P450. The straight route where TCE oxide does not proceed to phase II involves TCE oxide affecting the DNA adduct formation, DNA damage and mutation resulting to cancer. If it continues to phase II there is the likely chance of it turning into dichloroacetyl chloride and then dichloroacetic Acid. This acid can be excreted due to it being highly water soluble; it can also cause epigenetic changes and modifications in blood cells. 

Describe 1) the major route of exposure (absorption), 2) the primary target site (e.g. type of neuron) where toxic action takes place, and 3) the toxic mechanism of action of botulinum toxin (BTX).

The major route of exposure for botulinum toxin is oral, with the primary target site being the neurotoxin (peripheral, neuromuscular junction). The toxic mechanism of action begins by interfering with the acetylcholine when it fuses with the membrane within the neuromuscular junction. When BTX is present is cleaves the SNARE proteins(critical for membrane fusion and neurotransmitter release), preventing acetylcholine from attaching, causing loss in muscle contraction (paralysis). Inhibiting neurotransmitter release from pre-synaptic terminal by destroying SNARE proteins (proteins responsible for membrane fusion between neurotransmitter-containing vesicles and plasma membrane).

Describe 1) the major route of exposure (absorption), 2) the primary target site (e.g. type of neuron) where toxic action takes place, and 3) the toxic mechanism of action of tetanus toxin (TeNT).

The major route of exposure for tetanus toxin is through a puncture wound or cut by a contaminated object (intravenous), with the primary target site being the central nervous system and GABA. The toxic mechanism of action of TeNT begins once the Hc domain binds to gangliosides, facilitating the endocytosis of tetanus toxin into peripheral motor neurons at the neuromuscular junction. This selectively blocks the release of inhibitory neurotransmitters (GABA). Inhibiting neurotransmitter release from pre-synaptic terminal by destroying SNARE proteins (proteins responsible for membrane fusion between neurotransmitter-containing vesicles and plasma membrane).

Describe toxic mechanism of aflatoxin causing DNA mutation and cancer development in the liver.

The toxic mechanism of aflatoxin begins with the reactive intermediates in phase 1 metabolism (epoxide) binding to the macromolecules within the liver cells in, breaking down the structural integrity and cellular functions. These include macromolecules such as lipids, proteins, DNA and RNA. Aflatoxin B1 binds to DNA at the guanine base in liver cells, corrupting the genetic code that regulates cell growth, which can lead to potentially cancerous tumors.