Overview of Cancer and Mutations

Overview of Cancer

• Cancer is a general term for over 100 diseases.
• These diseases are characterized by abnormal and uncontrolled cell growth.
• Cancer cells are not immortal.
• Typical cells live approximately 40 generations.
• After this, cells accumulate excessive genetic errors, leading to cell death.
• Cancerous cells live longer, increasing the probability of error accumulation.

Cancer Terms

• Benign tumor: A non-invasive growth that may turn malignant.
• Malignant tumor: A cancerous growth that spreads to other parts of the body via the bloodstream or lymph nodes.

Mutagens vs. Carcinogens

• Mutagens cause alterations in genetic materials.
• Cancer cannot occur without a mutation.
• Mutations can occur without cancer.

Types of Mutations

• Point mutations: A single nucleotide is replaced with another. Some point mutations have no effect, while others do affect protein function.
• Frameshift mutations: One or more nucleotides are deleted, shifting the reading frame of the genetic code. This almost always results in a protein with different or no function.
• Other mutation types include: chromosome deletions, thymine dimers (caused by UV light), strand breaks (caused by X-rays/ionizing radiation), DNA adducts (caused by carcinogens), and oxidized bases (caused by oxidizing agents).

Carcinogens

• Carcinogens are compounds that induce severe DNA mutations, potentially leading to cancer.

Mutagen Screening (Ames Test)

• Uses Salmonella typhimurium bacteria.
• A reverse mutation test, where mutant bacteria are exposed to potential mutagens.
• If bacteria grow on a plate without the necessary nutrient (histidine), this indicates that the compound is a mutagen.
• Important for identifying mutagens and carcinogens.

Common Exposures to Mutagens and Carcinogens

• Polycyclic aromatic hydrocarbons (PAHs): released from combustion of fossil fuels and creosote-soaked wood.
• Nitrosamines: Found in saliva and some processed foods.

Common Carcinogenic Exposures

• Benzo[a]pyrene (PAH): Comes from incomplete combustion of organic compounds. Found in cigarette smoke, car exhaust, and certain foods.

Common Genotoxic Exposures

• Heterocyclic Amines (HCAs): Produced during the cooking of meat at high temperatures (above 180°C).
• Acrylamide: Formed when starchy foods like French fries and potato chips are cooked at high temperatures.

Common Carcinogen Exposures - Synergistic Effect

• Alcohol and smoking: Alcohol dissolves fats in membranes, allowing carcinogens in smoke to enter cells more easily, increasing the potential for damage

Bioactivation

• Some compounds become more toxic after being metabolized.
• Example of benzo[a]pyrene: it is metabolized via CYP450 enzymes in phase I and phase II reactions into a form that covalently binds to DNA.

Bioactivation Mutagenicity Test

• Tests to examine the mutagenic ability of a substance due to activation from metabolic processes in a living organism.

Teratogens

• Compounds that are only genotoxic to a developing fetus.
• Example: Thalidomide, used as a sedative in the 1950s, caused massive developmental defects in babies.

Molecular Cancer Progression Model

• Shows DNA changes leading to cancer from a normal cell to precancer to cancerous cell to metastasis.

Clinical Cancer Progression Model

• Focuses on cell/tissue morphology, growth rate, and cancer progression from normal to hyperplasia to localized cancer to invasive cancer to metastatic cancer.

Clinical Cancer Patterns

• Cancer can recur even after surgical removal.
• In some cases, the cells may dedifferentiate to indicate recurrence, while in other cases, cells appear normal but become cancerous suddenly.

Molecular Patterns in Cancer

• Multiple gene mutations cause cancer.
• Sequence of gene loss is specific and frequently starts with DNA repair and P53 gene, followed by growth suppressors and growth promoters, and ends with the loss of anchorage dependence.

Patterns of Cancer

• Cancer development is complex with multiple gene loss combinations.
• Different individuals might have different molecular bases for the same type of cancer.
• There's no universal cure for cancer.

Environmental Toxicologists

• Use animal experiments to study cancer development, from initiation to promotion to progression.

Initiation

• Creation of a neoplastic cell due to a mutation from a chemical interaction with DNA.
• DNA repair functions and apoptosis (cell death) attempt to reverse the damage, but mutations are permanent.

Promotion

• Neoplastic cell growth, often after a period of latency.
• The process is slow and involves repeated exposures to carcinogens. The damaged DNA repair mechanisms also contribute.

Progression

• Visible tumor formation, continuous genetic changes.
• Invasion into adjacent tissues, and spread to other body parts (metastasis).
• Loss of communication between cells.

Other Cancer Models

• Presents various models of cancer development: animal experiments, cell biology, molecular biology, and clinical/animal data to illustrate cancer progression details.

Problems with Research

• Latency periods (10-20 years).
• Lack of safe dosages.
• Satisfying all models for cancer study.
• Cure versus prevention.

Cure vs. Prevention

• Prevention has a higher potential for impacting cancer outcomes and death rates.

Cancer Rates

• Shows relative frequencies of different types of cancer in male and female populations in different regions.

Diagrams (Figures)

• Include pictures and diagrams of cell structure, DNA, and cancer progression models if available.

This quiz covers the fundamental concepts of cancer, including its definition, types of tumors, and the differences between mutagens and carcinogens. Additionally, it delves into the specifics of point and frameshift mutations, enhancing your understanding of genetic alterations related to cancer. Perfect for anyone studying biology or health sciences.