Cancer: Mechanisms of DNA Damage

Question 1

list 3 types of DNA damage that lead to carcinogenesis

Answer 1

• broken hydrogen bonds turning into covalent bonds
• double stranded breaks (translocation mutations)
• DNA adduct (chemical clusters of atoms that react with DNA)

Question 2

Some chemical carcinogens are _____ carcinogens whilst others require some form of _______ _______.

Answer 2

direct

metabolic activation

Question 3

chemical carcinogens were once used as

Answer 3

manufacture of dyes

Question 4

chemical carcinogens aromatic amines and aminoazo compounds contain

Answer 4

amino and azo groups which vary strongly carcinogenic and non-carcinogenic

Question 5

polycyclic aromatic hydrocarbons are

Answer 5

naturally occurring products from the incomplete combustion of nearly any organic compound (coal, tar, oil, meat, tobacco)

Question 6

polycyclic aromatic hydrocarbons are defined by their

Answer 6

polycyclic ring structure

Question 7

list 2 characteristics of N-nitro compounds

Answer 7

-industrial chemicals
-nitrates and nitrites are not carcinogenic but are converted to nitrosamines in the gastrointestinal tract

Question 8

alkylating agents are not defined by their chemical structure but by their

Answer 8

reactivity (ability to join a chemical group to another molecule)

Question 9

what is one mechanism of chemical carcinogens?

Answer 9

methylation

Question 10

describe methylation mechanism

Answer 10

a methyl group is added to a DNA base -> incorrect base pairing occurs -> subsequent base pairing now forms a normal pair that become permanent mutations and cannot be repaired

Question 11

how does UV damage DNA

Answer 11

by creating pyrimidine dimers in adjacent thymine’s. if not repaired it can cause improper base pairing during replication and downstream a permanent mutation that is formed and is capable of indefinite replication

Question 12

How does benzo[a]pyrene distort the double helix molecule?

Answer 12

benzo[a]pyrene interacts with cytochrome p450 in the liver creating an intermediate with an epoxide group. This reacts with guanine in DNA

Question 13

how does phorbol ester lead to cell proliferation

Answer 13

binding of external signal molecule leads to activation of phospholipase C -> phospholipase C cleaves membrane lipid PIP2 to produce DAG -> DAG activates protein kinase C triggering events that lead to cell division

Question 14

what determines the carcinogenic ability of phorbol esters?

Answer 14

the number and position of side chains
(alterations reduces affinity for binding PKC)

Question 15

what are the 2 ultimate outcomes of pathway mutations?

Answer 15

1. cell proliferation in excess
2. inhibit apoptosis