Mycotoxins and Their Metabolism

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.

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.