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Questions and Answers
What characterizes the growth of cancer cells?
What characterizes the growth of cancer cells?
Which of the following is true regarding precancerous cells?
Which of the following is true regarding precancerous cells?
What is metastasis in the context of cancer?
What is metastasis in the context of cancer?
Which of the following describes dysplasia?
Which of the following describes dysplasia?
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Which method does NOT contribute to the process of metastasis?
Which method does NOT contribute to the process of metastasis?
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What abnormal increase in cells is referred to as hyperplasia?
What abnormal increase in cells is referred to as hyperplasia?
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Which of the following is a critical factor in the development of tumors?
Which of the following is a critical factor in the development of tumors?
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What is the main toxic effect associated with aflatoxins?
What is the main toxic effect associated with aflatoxins?
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Which food products are commonly contaminated with aflatoxins?
Which food products are commonly contaminated with aflatoxins?
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What significant physiological effect does the aflatoxin B1-8,9-epoxide have?
What significant physiological effect does the aflatoxin B1-8,9-epoxide have?
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Which mycotoxin is known to have neurotoxic properties?
Which mycotoxin is known to have neurotoxic properties?
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What conditions lead to high levels of fumonisin production?
What conditions lead to high levels of fumonisin production?
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Which of the following mycotoxins is categorized as probably carcinogenic?
Which of the following mycotoxins is categorized as probably carcinogenic?
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What type of inflammation is associated with fusariotoxins?
What type of inflammation is associated with fusariotoxins?
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Which enzyme systems are involved in the metabolism of aflatoxins?
Which enzyme systems are involved in the metabolism of aflatoxins?
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What is the consequence of mutations in apoptosis genes?
What is the consequence of mutations in apoptosis genes?
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Which step in the cancer process is characterized as irreversible?
Which step in the cancer process is characterized as irreversible?
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What is a weak inducer of chemical carcinogenesis?
What is a weak inducer of chemical carcinogenesis?
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What happens to CYP1A1 activity in the absence of phytochemicals when PhIP is present?
What happens to CYP1A1 activity in the absence of phytochemicals when PhIP is present?
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Which process involves the accumulation of additional mutations and leads to malignant tumors?
Which process involves the accumulation of additional mutations and leads to malignant tumors?
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Which compound is primarily involved in the phase II glucuronidation reaction?
Which compound is primarily involved in the phase II glucuronidation reaction?
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How do vegetables interact with PhIP in terms of binding to AhR?
How do vegetables interact with PhIP in terms of binding to AhR?
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Mycotoxins are primarily produced by which organisms?
Mycotoxins are primarily produced by which organisms?
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Which of the following is NOT a noted characteristic of the cancer process?
Which of the following is NOT a noted characteristic of the cancer process?
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What is the result of the N-hydroxylation reaction of PhIP?
What is the result of the N-hydroxylation reaction of PhIP?
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What is one of the consequences of fast NAT1/NAT2 enzyme activity variants?
What is one of the consequences of fast NAT1/NAT2 enzyme activity variants?
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What is the role of chemical carcinogens like HCA and PAH in cancer development?
What is the role of chemical carcinogens like HCA and PAH in cancer development?
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What is the role of GST in the context of PhIP metabolism?
What is the role of GST in the context of PhIP metabolism?
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What impact do mutations in genes that promote cell proliferation have?
What impact do mutations in genes that promote cell proliferation have?
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What type of compound is PhIP classified as after undergoing metabolism?
What type of compound is PhIP classified as after undergoing metabolism?
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What is the consequence of CYP1A1/2 activity decreasing as a result of competitive inhibition?
What is the consequence of CYP1A1/2 activity decreasing as a result of competitive inhibition?
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What is primarily formed when HMF is metabolized in the human body?
What is primarily formed when HMF is metabolized in the human body?
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Which of the following best describes the classification of acrylamide by the IARC?
Which of the following best describes the classification of acrylamide by the IARC?
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How does acrylamide predominantly affect neurotransmission?
How does acrylamide predominantly affect neurotransmission?
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Which of the following statements about acrylamide’s excretion is true?
Which of the following statements about acrylamide’s excretion is true?
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What is one of the neurotoxic effects of acrylamide in humans?
What is one of the neurotoxic effects of acrylamide in humans?
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Which enzyme is associated with the metabolism of acrylamide to its reactive intermediate?
Which enzyme is associated with the metabolism of acrylamide to its reactive intermediate?
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What type of genetic variations may lead to higher levels of acrylamide-Hb adducts?
What type of genetic variations may lead to higher levels of acrylamide-Hb adducts?
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Which of the following is a genotoxic and mutagenic product formed from the metabolism of HMF?
Which of the following is a genotoxic and mutagenic product formed from the metabolism of HMF?
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What role do isothiocyanates (ITCs) play in relation to AhR?
What role do isothiocyanates (ITCs) play in relation to AhR?
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Which of the following statements about phytochemicals is true?
Which of the following statements about phytochemicals is true?
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What is the primary structure shared by all PAHs?
What is the primary structure shared by all PAHs?
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What is the significance of the 'bay region' in BaP metabolism?
What is the significance of the 'bay region' in BaP metabolism?
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Which phase of BaP metabolism leads to the formation of mercapturic acid in urine?
Which phase of BaP metabolism leads to the formation of mercapturic acid in urine?
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What is produced when BaP is metabolized to reactive epoxides?
What is produced when BaP is metabolized to reactive epoxides?
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Which enzyme plays a crucial role in the conjugation of BaP?
Which enzyme plays a crucial role in the conjugation of BaP?
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What is one characteristic of the parent compound of BaP?
What is one characteristic of the parent compound of BaP?
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What is the effect of competitive inhibition by ITCs on CYP activity?
What is the effect of competitive inhibition by ITCs on CYP activity?
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How does steric hindrance affect BaP metabolism?
How does steric hindrance affect BaP metabolism?
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Study Notes
NUTR*4510 Toxicology, Nutrition & Food - Unit 4: Chemical Carcinogens in Foods
- This unit covers chemical carcinogens found in foods.
Neurotoxicity Perspective
- Adverse effects affect brain, central nervous system, and peripheral nervous system functions
- Effects can be permanent or reversible
- Lipophilic xenobiotics accumulate in lipid-rich regions like the brain and spinal column
- Potential issues include problems with cognition, nerve transmission (action potentials and synaptic function), neurotransmitter function, sensory/perception, motor function, and behaviour/emotions
Neurotoxicity Phenotypic Manifestations/Characteristics
- Confusion, poor concentration, and memory loss are among the common symptoms
- Personality changes, behavioral changes, and pain (headache or localized)
- Numbness, hyperesthesia, and paraesthesia
- Loss of sensation, muscle weakness, loss of coordination
- Difficulty with speech/communication, swallowing
- Paralysis, involuntary muscle jerks or spasms, seizures
- Dizziness or vertigo; changes in sensory function (visual, auditory, taste, smell, touch)
- Changes in levels of consciousness, respiratory distress (rapid/slowed breathing/shallow breaths/asphyxiation), coma
- Cardiovascular effects (tachycardia, bradycardia, hypotension, pulmonary edema) and gastrointestinal effects (abdominal pain, diarrhea, vomiting)
Grading of Common Neurotoxicity Symptoms
- Grades I-IV categorize severity based on limiting activities of daily living (ADLs) and disorientation
- Grade I is mild limiting of ADLs and mild disorientation
- Grade II limits instrumental ADLs, and disorientation levels rise further
- Grade III severely limits self-care ADLs, and disorientation is severe
- Grade IV involves life-threatening consequences and urgent intervention
- This table serves to understand the varying grades of severity
Common Neurotoxicity Manifestations
- Encephalopathy is damage or malfunction in the brain causing an altered mental state, possibly with physical changes.
- Dysphasia leads to the inability to verbalize or understand speech
- Somnolence is the feeling of sleepiness or drowsiness
- Seizures are uncontrolled electric disturbances in the brain, manifesting as changes in behaviour, movement/spasms, or consciousness.
Basic Information about Cancer
- Cancer involves abnormal cell morphology (structure) and cell growth (proliferation)
- Many cells replicate continuously and unpredictably in cancer
- Cancer cells have variations in their sizes and shapes.
- The nucleus of a cancer cell is larger and darker than a normal cell nucleus.
- Clustered cancer cells lack a defined boundary.
What is Cancer?
- Cancer is a group of diseases with diverse types in varying tissues
- Cell growth and proliferation are controlled and highly regulated in healthy tissues
- Benign or malignant tumors can form, either of which can be either benign or malignant
Precancerous (Premalignant) Definitions
- Hyperplasia: An abnormal increase in cell numbers.
- Atypia (Atypical): Cells appear slightly abnormal under a microscope
- Metaplasia: Cells appear normal under microscopy, differing from normal tissue type
- Dysplasia: Cells exhibit abnormal organization and appearance, which might evolve into cancer over time
Metastasis
- Cancer cells spreading to other parts of the body to form new tumors
- Three methods of metastasis are invasion (direct extension), through the bloodstream (hematogenous spread), and through the lymphatic system
In Cancer
- Increased cell proliferation and decreased or blocked apoptosis are key characteristics
- This leads to the formation of long-lived, rapidly dividing cells, leading to tumors that grow in size and potentially metastasize
Examples of Types DNA Damage
- Base mismatch
- Point mutation (specific example provided)
- Single strand breaks
- Abasic sites
- 8-oxoguanine (mismatched base pairing)
- Double-strand breaks
- Cross-links (intrastrand and interstrand)
- Bulky adducts
- Small adducts
- Various types are identified
DNA Repair Mechanisms
- Primarily focuses on the base excision repair mechanism.
- Includes enzymes, stages, and mechanisms involved in the repair process
Examples of DNA Damage or Mutations Leading to Cancer
- Mutations in DNA repair mechanisms impede cells from fixing DNA damage.
- Example mutations in tumor suppressor genes, cell cycle genes, and apoptosis genes
- Changes in genes responsible for cell proliferation can result in an increased rate of replication.
Chemical Carcinogenesis Process
- Involves initiation (irriversible), promotion (encourages cell division), and progression (additional mutations, permanent changes) that lead to invasion and metastasis
- Specific examples of inducers are HCA, PAH, NA
- Ethanol is a weak inducer
- Accumulation of additional mutations are favored by heightened multiplication.
Examples of Types DNA Damage (continued)
- Focus on different types of DNA damages and repair mechanisms
Examples of Types DNA Damage (continued)
- Further detailed explanation of various DNA damages and repair processes.
Mycotoxins
- Toxic metabolites produced by molds/fungi; mycotoxins are a significant issue in many food sources
- Molds can grow before/after harvest or during food storage
- Often seen in warm, damp, or humid conditions
- Exposure is through eating infected foods or consuming animals that have consumed contaminated feed.
- Mycotoxins can significantly impact health both in humans and livestock, ranging from acute poisoning to long-term issues like immune deficiency and cancer,
Multistep Hepatocarcinogenesis
- Describes a stepwise development of liver cancer through hepatocytes, adenomas, and carcinomas
- Details methods of identifying and studying this process experimentally.
Examples of Dietary Carcinogens (perspective of xenobiotic metabolism)
- Mycotoxins
- Polycyclic aromatic hydrocarbons (PAHs)
- Heterocyclic amines (HCAs)
- Nitrosamines
PAH
- Polycyclic aromatic hydrocarbons are a class of over one hundred chemical compounds formed from incomplete combustion.
- These compounds form when burning various substances like food fats, carbohydrates, wood chips, tobacco, etc.
- They form at temperatures greater than 250 C
- PAH cause cancer in various parts of the gastrointestinal tract, primarily.
- Certain phytochemicals, like those found in many fruits and vegetables, compete with PAHs to prevent activation by the CYP family and binding to AhR.
HCA
- Heterocyclic amines, or HCAs, are a group of 20+ chemical compounds that contain heterocyclic and amine rings.
- They form during cooking processes like grilling, roasting, baking, and frying, resulting in high temperatures.
- The main source is the reaction between amino acids, sugars, and high temperatures within the cooking process.
HMF
- 5-Hydroxymethylfurfural (HMF)
- Potentially carcinogenic to humans, this material is a flavoring agent in several foods.
- HMF forms during Maillard reactions and caramelization via sugar dehydration.
- higher cooking temperature leads to higher HMF concentration.
- HMF concentration can be a marker to measure the quality of processed foods
- Intake range is 30 to 150 mg per day/person
Acrylamide
- Formed when certain amino acids (e.g., asparagine) react with reducing sugars during high temperature cooking
- Found in several different food items (e.g., potato chips, french fries, and other starchy/baked goods)
- Has been linked to neurotoxic properties in animals, but the association with humans is less clear.
PhIP
- PhIP (2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine), a heterocyclic amine that is formed during cooking of meat, fish, or chicken in the conditions of higher temperatures.
- PhIP can trigger enzymes called CYPs (Cytochrome P450) and AhR activation to increase the formation of reactive intermediates, ultimately promoting DNA damage.
- Vegetables can competitively prevent PhIP from binding to the AhR.
BaP Metabolism
- Metabolism involves a series of reactions starting from the intake of a chemical to various steps of excretion.
- The CYP1A1/2 family are key in the metabolism of BaP. This is related to their expression response to environmental factors or diet (many products and foods can induce).
Tobacco Xenobiotics & Review
- Describes the effects of nicotine and other toxins from tobacco.
- The effect is on the body's systems due to the intake or exposure.
- Nicotine is an insecticide and neurotoxin often present in tobacco.
- Nicotine-derived nitrosamine ketone (NNK) is a secondary carcinogen.
- Nitrate converts into nitrite, which can react with amines and form nitrosamines
Nitrosamines
- Formed by reaction of secondary or tertiary amines and nitrosating agents, like nitrite
- Common in processed meats, and some other food products (e.g., cured bacon, processed meats, non-fat dry milk, beer and certain types of fish).
- These compounds are linked to increased cancer risk as they cause mutations after interacting with DNA.
- Elevated risks associated with this compound are esophageal and gastric cancers.
Review Cytochrome P450 (CYP) enzymes
- Different types of CYPs are outlined based on their locations in the body and their specific function
- The table summarizes the tissue distribution, specific inducers (e.g., certain chemicals), nuclear receptors involved, and substrates/products.
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Description
This quiz explores Unit 4 of NUTR*4510, focusing on chemical carcinogens found in foods. It also examines neurotoxicity, discussing adverse effects on the brain and nervous system. Understand the phenotypic manifestations of neurotoxicity, including cognitive impairments and sensory dysfunction.
