Carcinogens

Question 1

What is carcinogen?

Answer 1

Agents that inflict genetic damage and can cause cancer

Question 2

What are the 3 classes of carcinogens

Answer 2

1. Chemical carcinogen
2. Radiation energy
3. Microbial products

Question 3

What carcinogen is typically a weak carcinogen?

Answer 3

Direct-acting agent

Question 4

What are the two types of chemical carcinogenesis

Answer 4

1. Direct-acting agent
   - require no metabolic conversion to become carcinogenic
2. Indirect-acting agent
   - require metabolic conversion

Question 5

What are some of the most potent indirect chemical carcinogens created with burning of fossil fuels, plants and animal material?

Answer 5

Polycyclic hydrocarbons

Question 6

Metabolic conversion of indirect-acting carcinogens to ultimate carcinogens are mediated by…….

Answer 6

Cytochrome P450-dependent monooxygenases

Question 7

Describe the mechanism of action of chemical carcinogens

Answer 7

• all directs and ultimate carcinogens contain highly reactive electrophile groups that form chemical adducts with DNA, RNA and proteins (can cause mutation)
• RAS and TP53 are usually responsible for carcinogenesis
• mutations induced by carcinogens are not entirely random

There are two stages:

1. Intitiation
   - initiating agents are mutagenic and tumourigenic
   - causes mutation to DNA
   - initiation alone is not sufficient for tumour formation
   - rapid & irreversible and has memory
2. Promotion
   - promoters are chemical agents that are not mutagenic but stimulate cellular proliferation of initiated cells
   - they are non-tumourigenic
   - do not affect DNA directly
   - reversible
   - to be effective, repeated or sustained exposure to promoter must follow the application of initiating agent

Question 8

Two types of radiation carcinogenesis

Answer 8

1. Ultraviolet rays
   - can cause skin cancers (melanoma, squamous cell carcinoma, basal cell carcinoma
   - UVB is responsible for induction of skin cancers
2. Ionizing radiation
   - electromagnetic (x-ray, gamma ray) and particulate (alpha particles, beta particles, protons, neutrons) are all carcinogens

Question 9

In mechanism of action of UV rays, it induces the formation of pyrimidine dimers within DNA. Which pathway can repair this type of DNA damage?

Answer 9

Nucleotide excision repair pathway

Question 10

Patients with xeroderma pigmentosum is predisposed to what kind of cancer? And why?

Answer 10

Skin cancer. Due to defect in the nucleotide excision repair pathway that is responsible for repair of DNA damage because of formation of pyrimidine dimers within DNA.

Question 11

What is the mechanism of action in ionizing radiation?

Answer 11

Ionizing radiation causes chromosomal breakage, chromosomal rearrangement (translocation and inversion), and point mutation