Semis toxicology

• Non-organ directed toxicity


  Toxicities that do not affect the organs but rather the cells, genes, and the developing fetus
• Types of non-organ directed toxicity

  • Chemical carcinogenesis
  • Genetic toxicology
  • Developmental toxicology

  
• Carcinogenesis


  Formation of cancer
• Cancer


  A disease of cellular mutation, proliferation, and aberrant cell growth resulting in malignant neoplasm
• Cancer should have all three characteristics: cellular mutation, proliferation, and aberrant cell growth
• Cancer ranks as one of the leading causes of death in the world
• 70-90% of human cancers are linked to environmental, dietary, and behavioral factors
• Neoplasia


  New growth or autonomous growth of tissues
• Neoplasm


  Resulting in neoplastic lesion
• Types of neoplasm


  • Benign
  • Malignant
• Benign neoplasm


  Expansive growth, frequently exhibiting slow rates of proliferation that do not invade surrounding tissue or other organs, localized growth
• Malignant neoplasm


  Invasive growth characteristics, capable of spreading through the organ of origin, and through metastasis to other tissues and organs
• Neoplasm nomenclature


  Reflects both the tissue and cell of origin and the characteristics of the type of tissues involved
• General rule for benign neoplasm

  Tissue of origin is frequently followed by the suffix "oma"
• General rule for malignant neoplasm


  Tissue of origin is frequently followed by the suffix "carcinoma" or "sarcoma"
• Carcinoma


  Derived from epithelial origin
• Sarcoma


  Derived from mesenchymal origin
• Metastases


  Secondary growths derived from the cells of the primary malignant neoplasm
• Tumor


  Describes a lesion that may or may not be neoplastic and is characterized by swelling or an increase in size
• Scientifically, a tumor does not automatically equal cancer. Tumor must be neoplastic and malignant to be considered cancerous
• Carcinogen


  Physical or chemical agents that causes or induces neoplasia (formation of cancer)
• Types of carcinogens


  • Genotoxic
  • Non-genotoxic
• Genotoxic carcinogens


  Interact physically with DNA resulting in mutation (change or damage the structure)
• Non-genotoxic carcinogens


  Modify gene expression but do not damage DNA, do not directly interact with DNA but may create a scenario that will make the DNA more susceptible to damage from other sources
• Features of genotoxic and non-genotoxic carcinogens

  • Genotoxic: Mutagenic, Tumorigenicity is dose responsive, No theoretical threshold
  • Non-genotoxic: Nonmutagenic, Threshold is reversible, Tumorigenicity is dose responsive, May function at tumor promotion stage, No direct DNA damage, Species, strain, tissue specificity
• Multistage carcinogenesis


  Process on how cancer is formed in the body, involves a series of definable and reproducible stages
• Stages of multistage carcinogenesis

  • Initiation
  • Promotion
  • Progression

  
• Initiation


  Defined as a stable, heritable change that is a rapid and irreversible process that results in carcinogen-induced mutation
• Initiators (Initiating agents)


  Chemical/physical agents that function at the initiation stage, lead to genetic changes including mutation and deletions by covalently binding to DNA and forming adducts
• Initiators (Initiating agents)


  • Polycyclic hydrocarbons
  • Nitrosamines
  • Biological agents (Virus)
  • Physical agents (X-ray, UV light)
• Genotoxic compounds can be divided into direct-acting and indirect-acting genotoxic compounds
• Direct-acting genotoxic compounds don't need to be metabolized to cause DNA damage
• Fixation of the initiation stage

  Occurs when DNA is not correctly repaired or incompletely repaired prior to DNA synthesis, can lead to inappropriate base pairing and/or formation of mutation
• Initiation requires one or more rounds of cell division for the "fixation" of the DNA damage
• Initiation by itself is insufficient to cause cancer
• Non-organ directed toxicity


  Toxicities that do not affect the organs but rather the cells, genes, and the developing fetus
• Types of non-organ directed toxicity


  • Chemical carcinogenesis
  • Genetic toxicology
  • Developmental toxicology

  
• Carcinogenesis


  Formation of cancer
• Cancer


  A disease of cellular mutation, proliferation, and aberrant cell growth resulting in malignant neoplasm
• Cancer should have all three characteristics: cellular mutation, proliferation, and aberrant cell growth