Carcinogenic agents

Carcinogenic agents

Carcinogenic agents

On this page

Chemical Carcinogens - The Poison Pantry

  • Mechanism: Multi-step process involving initiation (irreversible DNA damage/mutation) and promotion (clonal expansion of initiated cells).
  • Activation: Most are procarcinogens, metabolically activated by cytochrome P-450 monooxygenases (liver) into electrophilic ultimate carcinogens that form DNA adducts.

Key Agent → Associated Cancer:

  • Aflatoxins (Aspergillus): → Hepatocellular Carcinoma (HCC)
  • Alkylating Agents (chemo): → Leukemia/Lymphoma
  • Aromatic amines (textile dyes): → Bladder Cancer
  • Arsenic (wood preservatives): → Skin (Squamous Cell), Lung, Liver (Angiosarcoma)
  • Asbestos: → Lung Cancer > Mesothelioma
  • Cigarette Smoke: → Lung, Bladder, Pancreas, Esophagus
  • Ethanol: → Oropharynx, Esophagus (Squamous Cell), Liver (HCC)
  • Nitrosamines (smoked foods): → Gastric Cancer
  • Vinyl chloride (PVC): → Liver (Angiosarcoma)

image

⭐ Aflatoxin B₁ induces a signature G→T mutation in codon 249 of the TP53 gene, a molecular fingerprint for diagnosing aflatoxin-induced Hepatocellular Carcinoma.

Radiation Carcinogenesis - Sun's Sinister Side

  • UV Radiation (UVR): Primarily from sun exposure; non-ionizing.
    • Mechanism: Forms pyrimidine dimers (T-T, C-T) in DNA, distorting the helix.
    • Repair: Nucleotide Excision Repair (NER) pathway. Defects in NER lead to conditions like Xeroderma Pigmentosum (XP), with ↑ risk of skin cancer.
    • Cancers: Basal Cell Carcinoma (BCC), Squamous Cell Carcinoma (SCC), and Melanoma.

image

  • Ionizing Radiation: From medical sources (X-rays, CT scans) or occupational/environmental exposure (radon, nuclear).
    • Mechanism: Causes double-strand DNA breaks, primarily through generation of hydroxyl free radicals from water.
    • Cancers: Acute Myeloid Leukemia (AML), Chronic Myeloid Leukemia (CML), and Papillary Thyroid Cancer.

High-Yield Fact: Papillary carcinoma is the most common type of radiation-induced thyroid cancer, often seen years after head and neck irradiation.

Oncogenic Microbes - Viral & Bacterial Villains

  • DNA Viruses

    • HPV (Types 16, 18): E6 protein inhibits p53; E7 inhibits Rb. Causes cervical, anogenital, & oropharyngeal SCC.
    • EBV (Epstein-Barr Virus): LMP-1 protein acts as a constitutively active CD40 receptor, promoting B-cell proliferation. Linked to Burkitt & Hodgkin lymphoma, nasopharyngeal carcinoma.
    • HBV & HCV: Chronic inflammation and hepatocyte regeneration drive mutations. HBx protein (HBV) is directly oncogenic. Leads to hepatocellular carcinoma.
    • HHV-8 (KSHV): Causes Kaposi sarcoma by promoting angiogenesis and cell proliferation, especially in immunosuppressed states (e.g., AIDS).
  • RNA Virus

    • HTLV-1: Tax protein activates NF-κB, stimulating T-cell proliferation. Causes Adult T-cell Leukemia/Lymphoma (ATLL).
  • Bacteria

    • H. pylori: Chronic inflammation. CagA protein disrupts cell signaling, promoting proliferation. Causes gastric adenocarcinoma & MALT lymphoma.

⭐ EBV is classically associated with Burkitt Lymphoma, especially the endemic African type, which often presents with a jaw lesion. The translocation t(8;14) involving the c-MYC gene is a hallmark.

Oncogenic Viruses: Structure and Associated Cancers

High‑Yield Points - ⚡ Biggest Takeaways

  • Aflatoxins (Aspergillus) are strongly linked to hepatocellular carcinoma.
  • Alkylating agents from chemotherapy create a risk for secondary leukemia/lymphoma.
  • Aromatic amines (e.g., aniline dyes, tobacco smoke) are a major cause of bladder cancer.
  • Arsenic exposure is associated with squamous cell carcinoma of the skin, lung cancer, and liver angiosarcoma.
  • Asbestos is famously linked to bronchogenic carcinoma and mesothelioma.
  • Ionizing radiation is a significant risk factor for papillary thyroid carcinoma and leukemias.

Practice Questions: Carcinogenic agents

Test your understanding with these related questions

A 45-year-old woman is found to have multiple masses in her liver while performing abdominal ultrasonography for recurrent right upper quadrant abdominal pain. Biopsy of one of the masses discloses large plates of adenoma cells, which are larger than normal hepatocytes and contain glycogen and lipid. Regular septa, portal tracts, and bile ductules are absent. Which of the following is associated with this patient's condition?

1 of 5

Flashcards: Carcinogenic agents

1/10

Which carcinogen is associated with the following types of cancer?_____ Squamous Cell Carcinoma of Oropharynx and Upper EsophagusPancreatic CarcinomaHepatocellular Carcinoma

TAP TO REVEAL ANSWER

Which carcinogen is associated with the following types of cancer?_____ Squamous Cell Carcinoma of Oropharynx and Upper EsophagusPancreatic CarcinomaHepatocellular Carcinoma

Ethanol

browseSpaceflip

Enjoying this lesson?

Get full access to all lessons, practice questions, and more.

Start Your Free Trial