Carcinogenic Compounds

• Carcinogenic substances are all types of substances that can cause changes to the structure and function of body cells.
• The three types of carcinogens

  Chemicals

  Radiation

  Biological agent
• The 4 Carcinogenesis Stages

  cancer initiation > cancer promotion > malignance transformation > progression of maliganance
• Cancer Initiation is the genetic alteration in a single normal somatic cell due to point mutations in DNA/ chromosome
• Chromosome mutations can occur in form of deletion, duplication, translocation, anueploidy (extra/missing)
• Examples of direct carcinogen:

  • dimethyl sulphate,
  • dimethyl carbamyl chloride
• examples of indirect carcinogen (procarcinogen)

  • benzo(a)pyrene : tobaco
  • polycyclic aromatic hydrocarbon (PCAH) : incomplete meat combustion
• Cancer promotion are efforts to multiply abnormal cells amidst normal tissue
• If DNA damage is detected by the body, apoptosis of cells occurs to prevent cancer. If the damage / mutataion persits, proliferation of cells occurs promoting cancer development
• Malignance transformation are the genomic changes in which a population of mutation cells cannot be inhibited by the cell’s microenvironment, changing the nature of the cell to be maliganant.
• Malignant cell characteristic

  Increase of : growth ability, cell mobility, chemotaxis

  Invasive and capable of secreting lytic factor

  Mutated gene is pass off to offspring

  Structural abnormalities in the cell
• What is the process of malignance progression characterized by?

  Multiplication of transformed cells and metastases to other tissues/organs
• What are Polycyclic Aromatic Hydrocarbons (PAHs)?

  Organic compounds with carbon and hydrogen atoms in two or more aromatic rings
• What are some natural sources of Polycyclic Aromatic Hydrocarbons?

  Forest fires, petroleum seeps, and volcanoes
• What are some anthropogenic sources of Polycyclic Aromatic Hydrocarbons?

  Electric power generation, incineration, and combustion engines
• What is the maximum allowable concentration of the most toxic Polycyclic Aromatic Hydrocarbon in food?

  1 µg/kg body weight
• What is Benzo(a)pyrene (BaP) and its effects on the body? [PCAH]

  It is a toxic compound that is absorbed in the intestines and localized in fat and adipose tissue
• What is the plasma half-life of Benzo(a)pyrene?

  Less than 5 minutes due to rapid distribution to tissues
• How is Benzo(a)pyrene excreted from the body?

  Excreted in urine and feces, approximately 16% within 48 hours post-administration
• Benzo(a)pyrene can penetrate the placental barrier
• What is the concentration of Benzo(a)pyrene found in pet food?

  Approximately 18 µg/kg
• What is the biotransformation product of Benzo(a)pyrene?

  7,8-dihydroxy-9,10-epoxy-benzo[a]pyrene (BPDE)
• What are the effects of BPDE?


  It is an ultimate carcinogenic and immunogenic compound leading to lung adenoma and proximal tubule lesions
• Why is PCAH (including BaP) a global concern?

  It causes intoxication of aquatic animals in offshore oil drilling spill areas
• What are the effects of naphthalene on the eyes?

  It causes irritation, corneal damage, and cataracts
• What happens if a dog consumes one tablet of naphthalene?


  It can lead to vomiting, diarrhea, lethargy, tachypnea, and balance disorders
• What is the effect of larger doses of naphthalene?

  It can cause acute hemolysis
• Is naphthalene carcinogenic in humans?


  It is possibly carcinogenic in humans
• What is the detection threshold of naphthalene vapor by smell?


  0.08 ppm
• What are some sources of amino aromatic compounds?


  Industrial crop exhaust, tobacco smoke, and diesel exhaust
• What are examples of amino aromatic compounds?


  Aniline, 2-naphthylamine, and benzidine
• What are the effects of arylamine exposure?


  It can lead to lymph cell proliferation and tumors in the spleen, bladder, prostate, and epidermis
• What are nitroso compounds and their natural source?

  Nitroso compounds include nitrosamines and nitrosamides, with natural sources like nicotiana tabacum
• What was N-nitrosodimethylamine used for?


  It was used as an antioxidant, lubricant, and rocket fuel
• What is the maximum nitrite preservative allowed in processed meat products?


  125 mg/kg
• What types of cancer can nitroso compounds cause in animals?


  Cancer in the liver, kidney, and lung
• What are alkylating agents and their historical significance?


  They are anticancer compounds with carcinogenic effects, such as nitrogen mustard used in WWI
• What are examples of alkylating agents?


  Cyclophosphamide, chlormethine, and busulfan
• How do alkylating agents cause cancer?


  They directly cross-link with DNA, causing DNA damage and inhibiting cell proliferation
• What is diethylstilbestrol and its uses?


  It is a synthetic nonsteroidal estrogen used for menopause therapy and as an animal growth promoter