Carcinogenesis

Question 1

Major categories of carcinogens

Answer 1

Chemicals, Radiation, Viruses, Parasites, Fungi

Question 2

Initiation of Carcinogenesis

Answer 2

Exposure to Carcinogen

Involves cellular genome mutations in tumour suppressor and oncogenes

Question 3

What happens after the promotion stage of carcinogenesis?

Answer 3

A new phenotype emerges resulting in clonal expansion of the pre-neoplastic focal lesion/initiated cell, leading to malignant metastases

Question 4

Progression Stage (Carcinogenesis)

Answer 4

Irreversible enhancement/repression of gene expression. Selection of neoplastic cells for optimal growth genotype in response to the cellular environment

Question 5

What is the latent period in carcinogenesis?

Answer 5

The timepoint between a dose of carcinogen and the occurrence of cancer

Question 6

Describe the Relationship between asbestos and mesothelioma

Answer 6

1. When inhaled, asbestos fibres become coated in proteins and excites an immune response called ASBESTOSIS
2. Asbestosis predisposes to bronchogenic carcinomas, increasing risk by a factor of 5
3. 25-45 years latent period

Question 7

Describe the relationship between smoking and cancer

Answer 7

ACTIVE CARCINOGEN: Polycyclic Aromatic Hydrocarbon 3,4-Benzpyrene

This molecule is converted by AHH enzymes, which is upregulated in smokers, to a substance that damages DNA directly

Question 8

How are carcinogens detoxified in the human body?

Answer 8

1. Glutathione S Transferase 1 detoxifies carcinogens; this is null in 30-50% of people. and they have a higher risk of cancer.
2. AHH may not be expressed so DNA-binding epoxides are not generated

Question 9

What is the increased risk percentage of cancer through passive smoking?

Answer 9

15-24% increased risk.

Question 10

Describe the effect of dietary carcinogens on the human body

Answer 10

1. NITRITES/NITRATES form a pathway for the conversion of dietary nitrites and nitrates to carcinogens
2. FOOD ADDITIVES (eg Fertilisers) that enter drinking water can get converted by gut bacteria into NITROSAMINES (carcinogens that lead to cancer of the GI tract/liver)
3. AFLAXOTOXICOSIS from certain strains of fungi (mould) is a potent carcinogen, especially in the liver

Question 11

Where is BCL2 expressed?

Answer 11

Crypts of colonic epithelium

Question 12

What is the function of BCL2?

Answer 12

Protects damaged cells from dying, so OVEREXPRESSION OF BCL2 leads to cell accumulation and tumorigenesis

Question 13

Describe the relationship between UV Light and cancer

Answer 13

UV Light can damage DNA, but this is normally fixed by DNA Repair/Cell Apoptosis, but repair-deficient individuals are particularly at risk

Question 14

Xeroderma Pigmentosum

Answer 14

A rare autosomal disease involving an inherited deficiency of endonuclease (for thymine dimer removal) so repair is inneffective.

Affected children show severe skin abnormalities and need protection from sunlight.