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Carcinogenic Agents (Radiation (UV Rays from :sunny: (3 TYPES (UVB = "…

- - - - UVB = "Burn"
        (cause of most skin cancers)
      - UVC
        (most potent carcinogen, but absorbed by Ozone)
      - UVA = "Aging"
        (penetrates deeply; Photoaging; skin cancer risk)
    - - UV Damage
        
        Covalent Bonds btwn Pyrimidine bases (Pyrimindine Dimers)
        
        Nucleotide Excision Repair fixes errors
        :cancer:when repair pathway overwhelmed
        
        EX: Xeroderma Pigmentosum
- - - - E6 ---- :forbidden:p53
      - E7 ---- :forbidden:Rb
  - - - :cancer:Burkett Lymphoma
        t(8;14) = dysregulated MYC next to Ig heavy chain
        90% endemic; 15% sporadic
      - :cancer:Nasopharyngeal Carcinomas
        LMP-1 not MYC translocations
      - :cancer:B-Cell Lymphoma (immunosupp.)
        LMP-1 not MYC translocations
        CD8+ cells can kill these cells if functioning
        
        :cancer:Diffuse Large B-Cell Lymphoma
        
        :cancer:Classic Hodgkin Lymphoma
      - :cancer:Hodgkin Lymphoma (subset)
- - - - Indirect Acting Carcinogens :star2: most common
        (require metabolic conversion to be carcinogenic)
        CYP450 required to metabolize; polymorphisms aff. risk
        
        :red_cross:Polycyclic Aromatic Hydrocarbons
        (soot, tar, oils, fuels, benzo[a]pyrene, form DNA adducts)
        :cancer:squamous cell carcinoma
        (of scrotum in ex w/ chimney sweeps)
        
        :red_cross:Aromatic Amines & Azo Dyes
        (aniline dye & rubber industry)
        :cancer:bladder cancer
      - Direct Acting Carcinogens
        (no metabolic conversion)
        
        EX: :red_cross:Alkylating Agents in Chemo
      - Initiator Chemical Carcinogens
        targeting particular DNA sequences
        
        :red_cross:Aflatoxin
        Aspergillus Flavus
        :cancer:hepatocellular carcinoma
        TP53 mutation
        
        :red_cross:Cigarette Smoke
        :arrow_up:mutations & particular base substitution = "smoking gun"
        (proving cancer related to smoking)
    - - :red_cross:Chronic Inflammatory Disease
        :arrow_double_up:cytokines & mitotic activity
      - :red_cross:Unopposed Estrogen