Cancer: Mechanisms of DNA Damage Flashcards
list 3 types of DNA damage that lead to carcinogenesis
- broken hydrogen bonds turning into covalent bonds
- double stranded breaks (translocation mutations)
- DNA adduct (chemical clusters of atoms that react with DNA)
Some chemical carcinogens are _____ carcinogens whilst others require some form of _______ _______.
direct
metabolic activation
chemical carcinogens were once used as
manufacture of dyes
chemical carcinogens aromatic amines and aminoazo compounds contain
amino and azo groups which vary strongly carcinogenic and non-carcinogenic
polycyclic aromatic hydrocarbons are
naturally occurring products from the incomplete combustion of nearly any organic compound (coal, tar, oil, meat, tobacco)
polycyclic aromatic hydrocarbons are defined by their
polycyclic ring structure
list 2 characteristics of N-nitro compounds
-industrial chemicals
-nitrates and nitrites are not carcinogenic but are converted to nitrosamines in the gastrointestinal tract
alkylating agents are not defined by their chemical structure but by their
reactivity (ability to join a chemical group to another molecule)
what is one mechanism of chemical carcinogens?
methylation
describe methylation mechanism
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
how does UV damage DNA
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
How does benzo[a]pyrene distort the double helix molecule?
benzo[a]pyrene interacts with cytochrome p450 in the liver creating an intermediate with an epoxide group. This reacts with guanine in DNA
how does phorbol ester lead to cell proliferation
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
what determines the carcinogenic ability of phorbol esters?
the number and position of side chains
(alterations reduces affinity for binding PKC)
what are the 2 ultimate outcomes of pathway mutations?
- cell proliferation in excess
- inhibit apoptosis