Carcinogenesis Flashcards
Define carcinogen
A carcinogen is a substance or agent capable of causing cancer by altering the genetic structure of cells.
Define initiator in chemical carcinogenesis.
An initiator is a mutagenic agent that causes permanent genetic changes (mutations) in oncogenes or tumor suppressor genes.
Define promoter in chemical carcinogenesis.
A promoter is a non-mutagenic agent that stimulates proliferation of initiated (mutated) cells, aiding progression toward cancer.
Define latent period in carcinogenesis.
The latent period is the time between exposure to a carcinogen and the clinical appearance of cancer.
What tumor is associated with asbestos exposure?
Mesothelioma (from blue asbestos) and bronchogenic carcinoma (asbestosis-related).
What tumor is associated with UVB radiation?
Basal cell carcinoma, squamous cell carcinoma, and melanoma.
What tumors are associated with ionising radiation?
Leukaemia, thyroid carcinoma (especially in children), and bone cancer.
What tumor is associated with aflatoxin B1?
Hepatocellular carcinoma (liver cancer), especially in areas with hepatitis B co-infection.
What tumor is associated with 2-naphthylamine?
Transitional cell carcinoma (bladder cancer).
What tumor is associated with benzpyrene (benz[a]pyrene)?
Lung cancer (from tobacco smoke), especially squamous cell carcinoma.
How does 2-naphthylamine cause bladder cancer?
It’s a pre-carcinogen activated by the liver to a carcinogenic metabolite (2-amino-naphthol), detoxified in liver but reactivated in bladder by β-glucuronidase into o-aminophenol which damages urothelial DNA.
What organ systems are involved in 2-naphthylamine metabolism and activation?
Liver (activation), kidneys (excretion), bladder (reactivation and damage).
What is the increased risk of lung cancer in smokers compared to non-smokers?
About 1:22.
Which genes are commonly mutated in smoking-induced lung cancers?
K-Ras and p53.
What is the carcinogen in tobacco smoke that causes DNA damage?
Benz[a]pyrene, metabolized by Aryl Hydrocarbon Hydroxylase (AHH) to a DNA-damaging diol epoxide.
What role does GSTM1 play in cancer risk among smokers?
GSTM1 detoxifies carcinogens; null genotype (no enzyme activity) increases lung and bladder cancer risk.
How does passive smoking affect cancer risk?
It increases risk of lung cancer; secondhand smoke causes ~11,000 deaths per year in the UK
Why is colon cancer more common than small intestine cancer?
The Bcl2 gene is expressed in the colon, suppressing apoptosis, allowing damaged cells to survive and accumulate mutations.
Is Bcl2 expressed in the small intestine?
No, it’s absent, so damaged cells undergo apoptosis, preventing mutation accumulation.
Who linked scrotal cancer to occupational exposure?
Percival Pott (1775), linking it to soot exposure in chimney sweeps.
What is the effect of high vs low doses of carcinogen?
High doses can act as both initiator and promoter, causing tumors. Low doses require a promoter to induce tumors.
What causes UV-related DNA damage?
Pyrimidine dimers, especially thymine dimers, leading to mutations if unrepaired.
What condition exemplifies UV repair deficiency?
Xeroderma pigmentosum – deficient in endonuclease needed for repairing UV damage.
How does radiation exposure cause cancer?
Causes DNA strand breaks and mutations; e.g., thyroid cancer post-Chernobyl, leukaemia in A-bomb survivors.
