Lecture 2 Flashcards
Ch. 2.1-2.3 DNA structure, mutations and carcinogenic agents
What are pyrimidines and what do they look like?
They include T and C and have 1 ring
What are purines and what do they look like?
They include A and G and have 2 rings
What does Thymidine include?
The base and the sugar
How many Hydrogen bonds to G and A form?
G forms 3 H-bonds, A forms 2 H-bonds
What are nucleosomes?
It has DNA wrapped around histones (8 in total) twice
When are chromosomes condensed?
After duplication but before division
What is the start codon?
ATG (forms Met)
What are the stop codons?
TAA, TAG, TGA
What is immature RNA
When the DNA is only transcribed and not yet spliced
How is DNA transcribed?
By RNA polymerase II binding to TF
What is extrachromosomal DNA?
It is circular, it promotes cell proliferation and is created when DNA divides without a centromere. The DNA is replicated, but unevenly distributed over the daughter cells
Which cells produce ROS?
Mitochondria and neutrophils
What causes exogenous DNA damage?
UV, smoke, alcohol, radiation
What types of radiation are included in ionizing radiation?
X-ray and gamma radiation
What causes indirect damage of DNA?
ROS hydrolysing water, which created an OH
How is 8-oxo-guanine created?
By having an OH attached to Guanine
What is the concequence of 8-oxo-guanine?
The G will be misread, leading to a point mutation
What is LET?
Linear Energy Transfer, the rate of energy loss along the track of an ionizing particle
What does a high LET mean
There is a high energy deposit, but low penetration
Which types of radiation have a low LET?
X-ray, gamma, protons
Which types of radiation have a high LET?
a-particles, neutrons, carbon ions
What does a higher LET mean in terms of Gy?
More cells are killed per Gy (Joule/kg)
What is ionizing radiation used for?
To kill tumors
What do you need for a carcinogenic risk estimation?
A large radiation exposed group, a non-exposed control, long follow-up time, individual dosimetry
What type of cancer is most frequently caused by ionizing radiation?
Leukemia, have a higher risk of solid cancers
How does the carcinogenic non-ionizing radiation UV work?
Forms pyrimidine dimers. Attaching 2 C below each other in the helix, which disturbs the helix. Polymerase cannot read the 2 C’s well and does point mutations here
What is the most effective UV carcinogen?
UVB
What are genotoxic chemical carcinogens?
The link to DNA, get DNA adduct formation, is not well recognised by polymerase, so mistakes are made
What are examples of genotoxic chemical carcinogens?
Polycyclic Aromatic Hydrocarbons: naphthalene
Aromatic amines: benzidine
Nitrosamines: NNK (tabacco, G to A)
Alkylating drug: chlorambucil
What are examples of other carcinogens?
Fibrous minerals, oncovirus, hormones, endogenous sources
