Mycotoxins and Their Metabolism

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Questions and Answers

What is the role of BaP in relation to the AhR?

BaP forms a stable complex with GSH for excretion.

BaP enhances the binding affinity of CYP1A.

BaP deactivates the AhR to prevent gene expression.

BaP binds to and activates the AhR to induce CYP1A family gene expression. (correct)

What is the consequence of BaP being lipophilic?

It may accumulate in lipid-rich tissues. (correct)

It prevents enzyme activation in metabolic pathways.

It enhances the binding of AhR to phytochemicals.

It facilitates rapid excretion in urine.

How is the reactive epoxide electrophile formed from BaP significant in metabolism?

It increases the availability of GSH for detoxification processes.

It produces a short-lived compound that quickly reacts in the body. (correct)

It reduces the risk of DNA damage by preventing accumulation.

It acts as a precursor for the formation of GSH conjugates.

What happens to the nucleophile diol intermediate in metabolism?

It is quickly metabolized to a reactive diol epoxide electrophile. Signup and view all the answers

What challenge is associated with the conjugation of the reactive diol epoxide electrophile?

It cannot be conjugated to GSH due to stearic hindrance. Signup and view all the answers

What is the most potent mycotoxin mentioned?

Aflatoxin Signup and view all the answers

Which health effects can be caused by mycotoxins?

Liver damage and cancer Signup and view all the answers

Under what condition is the risk of high levels of fumonisin particularly increased?

Hot, dry weather followed by high humidity Signup and view all the answers

Which type of food is commonly contaminated with aflatoxins?

Peanuts and grains Signup and view all the answers

What is one possible effect of mycotoxins on DNA?

Binding and damaging guanine/cytosine regions Signup and view all the answers

Which compound is primarily formed during the metabolism of HMF?

5-hydroxymethylfurfuroic acid Signup and view all the answers

What is the likely health effect of ochratoxin exposure?

Nephrotoxicity and potential carcinogenic effects Signup and view all the answers

How can mycotoxins affect protein function?

By binding to lysine residues and altering function Signup and view all the answers

What are the potential effects of the ester formed from the metabolism of SMF?

Genotoxic and mutagenic Signup and view all the answers

What is a potential consequence of widespread mycotoxin-induced cell apoptosis in a tissue?

Adverse effects on tissue function Signup and view all the answers

What is a common acute effect of exposure to substances like Zearalenone and Deoxynivalenol?

Nausea and vomiting Signup and view all the answers

How was acrylamide classified by the International Agency for Research on Cancer (IARC)?

Probably carcinogenic to humans Signup and view all the answers

What mechanism does acrylamide use to exert its neurotoxic effects?

Direct inhibition of neurotransmission Signup and view all the answers

Which CYP family is primarily induced by polycyclic aromatic hydrocarbons (PAHs)?

CYP1A Signup and view all the answers

What kind of food is primarily associated with fumonisins?

Corn and other grains Signup and view all the answers

What do phytochemicals do in relation to Benzo(a)pyrene (BaP)?

Compete for CYP activation and AhR binding Signup and view all the answers

Which of the following is a biomarker for acrylamide exposure?

Acrylamide-Hb adducts Signup and view all the answers

What is one of the primary health threats posed by mycotoxins to livestock?

Reduced milk production Signup and view all the answers

What is a potential reproductive effect of acrylamide based on studies in rodents?

Reduced sperm counts Signup and view all the answers

Which environmental factor is required for the formation of polycyclic aromatic hydrocarbons (PAHs)?

Burning materials at temperatures greater than 250°C Signup and view all the answers

What is one of the substrates of the CYP1A2 enzyme?

Aflatoxin Signup and view all the answers

Which cytochrome P450 enzymes are involved in acrylamide metabolism?

CYP 2E1 and CYP 1A2 Signup and view all the answers

What symptoms may result from sub-chronic low-level exposure to acrylamide?

Ataxia and gait abnormalities Signup and view all the answers

What effect do regular exposures to substances inducing CYP1A family have on cancer risk?

Increase bioactivation, leading to higher cancer risk Signup and view all the answers

Which receptors are involved in the binding of polycyclic aromatic hydrocarbons (PAHs)?

Aryl hydrocarbon receptors (AhR) Signup and view all the answers

Which of the following is NOT a characteristic of Zearalenone?

Enhances appetite Signup and view all the answers

Which mycotoxin is particularly hazardous when inhaled?

Zearalenone Signup and view all the answers

In which type of climate is aflatoxin exposure especially concerning?

Hot, humid climates Signup and view all the answers

What is a common symptom of acute liver injury associated with aflatoxin exposure?

Nausea Signup and view all the answers

What is the primary form of aflatoxin found in contaminated crops?

AFB1 Signup and view all the answers

What severe effect is associated with zearalenone exposure in addition to respiratory issues?

Skin blisters Signup and view all the answers

What is the effect of preventing the accumulation of reactive epoxide electrophile in the context of BaP metabolism?

It reduces the induction of CYP1A1/2 expression. Signup and view all the answers

Which compound is formed as a fast-reacting metabolite in BaP metabolism?

BaP-7,8-diol-9,10 epoxide Signup and view all the answers

What role does GSH/GST play in BaP metabolism?

They are involved in phase II detoxification. Signup and view all the answers

How does steric hindrance affect the metabolism of BaP?

It restricts access to the ‘bay region’ of the molecule. Signup and view all the answers

What is true about the characterization of BaP according to the content?

BaP acts as a stable secondary carcinogen. Signup and view all the answers

Which of the following best describes the outcome of limited phase II activity in BaP metabolism?

Enhanced initiation of genetic mutations. Signup and view all the answers

What is indicated by a 'fast reactive' designation in the context of diol metabolites?

They quickly bind to various targets in the body. Signup and view all the answers

Which of the following statements reflects the nature of the ‘bay region’ concerning BaP?

It undergoes significant steric hindrance during metabolism. Signup and view all the answers

Study Notes

NUTR*4510 Toxicology, Nutrition & Food - Chemical Carcinogens in Foods

Unit 4 focuses on chemical carcinogens in food, examining neurotoxicity as a preliminary perspective before discussing cancer.

Neurotoxicity Perspective

Adverse effects target brain, central nervous system, and peripheral nervous system structure/function.
Effects can be permanent or reversible.
Lipophilic xenobiotics accumulate in lipid-rich body regions (e.g., brain, spinal column).
Potential problems include cognitive impairments, nerve transmission issues (action potentials, synaptic function), neurotransmitter dysfunction, sensory and motor function problems, and behavioural/emotional abnormalities.

Neurotoxicity Phenotypic Manifestations

Confusion, poor concentration, and memory loss are possible symptoms.
Personality changes, behavioral changes (mood, activity), pain (headache or localized).
Numbness, hyperesthesia (excessive skin sensitivity), paraesthesia (tingling), loss of sensation, muscle weakness, coordination loss (ataxia), difficulties with speech/communication/swallowing are possible symptoms.
Paralysis, involuntary muscle jerks/spasms, and seizures/vertigo can occur.
Changes in sensory function (visual, auditory, taste, smell, touch), altered consciousness levels, respiratory distress (rapid/slowed breathing etc.), coma may, also, be seen.
Cardiovascular effects (tachycardia, bradycardia, hypotension, pulmonary edema) and gastrointestinal effects (abdominal pain, diarrhea, vomiting).

Grading of Common Neurotoxicity Symptoms

Grading of symptoms is assessed based on a scale (CTCAE 4.03).
Grades reflect varying degrees of symptom severity and impairment of daily activities (ADL).
Encephalopathy indicates brain damage or malfunction resulting in altered consciousness and physical changes.
Dysphasia refers to impaired speech or comprehension of speech.
Somnolence refers to feeling sleepy or drowsy.
Seizures involve uncontrolled electrical disturbances in the brain, presenting as behavioral, movement, or consciousness changes.

Basic Information about Cancer

Cancer involves abnormal cell morphology (structure) and abnormal cell growth (proliferation).
Normal cells divide and grow in a regulated manner.
Cancerous cells have variations in size, shape, and nucleus, often larger and darker than normal.
The number of chromosomes within cancerous cells may be abnormal.
Cancerous cells can cluster without boundary.

What is Cancer?

Cancer is a group of more than 100 different diseases affecting various tissues.
It's characterized by abnormal cell growth and division.
Benign and malignant tumors exist.
Precancerous conditions (premalignant cells) are abnormal cells that may become cancerous.
Some cells may undergo apoptosis to limit abnormal growth.

Precancerous (Premalignant) Definitions

Hyperplasia: an abnormal increase in the number of cells.
Atypia (atypical): cells look slightly abnormal under a microscope.
Metaplasia: cells look normally under a microscope, but are not the typical cell type found in that tissue.
Dysplasia: cells have abnormal appearance and organization, and may develop into a tumor over time.

Metastasis

Metastasis is the process of cancer cells spreading to other parts of the body, forming new tumors.
This can occur through invasion (direct extension to surrounding tissues), the bloodstream (hematogenous spread), and the lymphatic system.

In Cancer

Increased cell proliferation occurs.
Decreased or blocked cell apoptosis occurs.
Prolonged survival of transformed cells lead to tumors.
Tumors increase in size and can spread to other tissues (metastasis).

Examples of DNA Damage

Base mismatches, insertions/deletions, single-strand breaks, abasic sites, 8-oxoguanine formation are part of DNA damage.
Point mutations (e.g., G→T), are considered common but not the only form of potential damage.
DNA adducts, double-strand breaks and interstrand crosslinks are also examples of potential damage
Adducts refer to the binding of a segment of DNA to another structure.

DNA Repair Mechanisms

Base Excision Repair (BER) is the most common primary mechanism.
It fixes damaged DNA by removing and replacing damaged bases.
Enzymes like DNA glycolase and DNA polymerase play crucial roles in this process.
Nucleotide Excision Repair (NER), Mismatch Excision Repair (MER), and Double-Strand Break Repair (DSBR) are other important mechanisms for repair.

Examples of DNA Damage or Mutations Leading to Cancer Development

Mutations that impair DNA repair mechanisms prevent cells from fixing DNA damage.
Mutations in tumor suppressor genes disrupts the normal process of cell division and repair, leading to uncontrolled cell growth.
Mutations in cell cycle genes can cause cells to continue dividing uncontrollably.
Mutations in apoptosis genes lead to an excess of long-lived cells.
Mutations in cell proliferation-promoting genes lead to an increase in cell growth.

Chemical Carcinogenesis Process

Carcinogens induce DNA damage, leading to mutations.
They impact cellular processes including initiation, promotion, progression, and invasion/metastasis.

Multistep Hepatocarcinogenesis

A stepwise process, involving multiple mutations that lead progressively to hepatocellular cancer, starting with altered liver cells.

Mycotoxins

Mycotoxins are toxic metabolites produced by molds or fungi.
They can be present in various foods (crops, grains, nuts, spices, oilseeds).
Mycotoxins can cause acute or chronic adverse health effects, notably ranging from poisoning and immune deficiency to cancer.

Polycyclic Aromatic hydrocarbons (PAHs)

Formed through incomplete combustion of organic material.
Found in cooked meat, certain processed foods, and also in cigarette smoke.
They can induce cellular changes involved in many cancer types.
Various phytochemicals in fruits and vegetables (e.g. indole-3-carbinol) compete with particular PAHs to occupy cellular pathways.

Heterocyclic Amines (HCAs)

Formed through Maillard reactions (amino acids and sugars reacting during high-temperature cooking).
Found in meat, fish and poultry cooked via grilling. roasting, baking or frying.
They can induce cellular changes involved in many types of cancer.
Phytochemicals (e.g., indole-3-carbinol and others from vegetables) competitively bind to particular cell receptors.

5-Hydroxymethylfurfural (HMF)

Formed via Maillard reactions (specifically from carbohydrate-rich food products).
It can be used to measure food quality via its levels.
This marker is often found in processed foods.

Acrylamide

Formed from amino acids and sugars during high-temperature cooking of starchy foods.
It affects the nervous system and is considered a reproductive toxicant.

Tobacco Xenobiotics (Review)

Nicotine is a tobacco plant-produced neurotoxin.
Nitrogen is converted into ammonia before nitrate then nitrite in plants.
Heating, fermentation or curing of tobacco products can create a secondary and stable carcinogen (NNK).
NNK and other related substances negatively impact cellular functions and are associated with various cancer types.

Nitrosamines

Formed from amines and nitrites.
Nitrites are commonly used preservatives in food.
Nitrosamines, such as DMN, are cancer-causing compounds (carcinogens in rats).

Dimethylnitrosamine (DMN)

A highly stable and well known nitrosamine.
It has a known impact on human health resulting in liver damage, and possibly increasing liver cancer risk.

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Description

This quiz examines the effects of mycotoxins and their metabolic pathways, focusing on compounds like BaP and HMF. Learn about their interactions with health, including potential DNA damage and protein function impairment. Test your knowledge on the consequences of exposure and the conditions that increase risks associated with mycotoxins.