27th Jan - Properties of Cancer Cells Flashcards
What percentage of human cancers are of epithelial origin?
85%
Why do epithelial cells have the highest rate of cancer transformation?
Epithelial cells are the first exposed to any mutagens as they line external and internal surfaces
What are the two main components of environmental causes of cancer?
Infectious Agents
Lifestyle
Where does the main evidence for environmental causes of cancer come from?
Epidemiology - v. different cancer prevalence based on geographic location, and cancer rates in migrants become similar to that of the population
What percentage of worldwide cancer deaths is attributed to infectious agents?
20%
Give 5 examples of viruses that cause cancer in humans
Epstein Barr virus Heptatitis B virus Human T-lymphocytic virus-1 HPV16 and HPV18 Hepatitis C virus
What cancers can be caused by the Epstein Barr Virus?
Burkitt's lymphoma Nasopharanygeal carcinoma Lymphoproliferative disorder Some Hodgkin's Some non-hodgkins GI lymphoma
What cancers can be caused by the hepatitis B virus?
some Hepatocellular carcinomas
What cancers can be caused by the hyman T-lymphotropic virus -1?
Adult T-cell leukaemia
What cancers can be caused by HPV16 and HPV18?
Most cervical cancers
Most penile cancers
Angogenital cancers
Head and neck cancer
What cancers can be caused by the Hepatitis C virus?
Some hepatocellular carcinomas
Some lymphomas
Name a bacteria that can cause cancer
Helicobacter pylori can cause gastric carcinoma
What are the key lifestyle factors that can cause cancer?
Smoking, diet, reproductive hormones, alcohol, ionising radiation and infection
What are tumour promoters?
Agents in the environment that do do not damage DNA but promote cell proliferation
What are tumour initiators?
Agents in the environment that cause DNA damage
Outline an experiment that shows how promoters and initiators work together to cause cancer
Painted initiators and promoter on mouse and monitored effects for 3 months
Paint once w/ initiator -> No effect
Multiple paintings once w/promoter –> No change
Paint once w/ initiator –> Multiple w/ promoter –> papilloma
Paint once w/ initator –> multiple w/ promoter in different region–> no change
1st initiator, then promoter –> papilloma –> stop promoter painting –> no tumour
1st initiator, then promoter –> papilloma –> keep painting w/ promoter extensively –> stop painting –> papilloma
1st initiator, then promoter –> papilloma –> paint w/ initiator –> Carcinoma
Give examples of human tumour promoters and the cancer they promote
Oestrogen --> Endometrium Oestrogen and progesterone --> breast Diuretics --> kidney Hepatitis B/c virus --> liver Bile --> small intestine Gall stones --> gall bladder
Give examples of chemical carcinogens
Polycyclic aromatic hydrocarbons
Aromatic amines
A20 dyes
Give examples of ionizing radiation
Atomic particles
X-rays
UV
What is the role of cytochrome p-150 in cancer?
It is a chemical carcinogen which converts PAHs into ultimate carcinogens (BPDE)
How does UV exposure –> cancer?
It causes mutations by creating pyrimidine dimers
How do you test for DNA damage?
the Ames test
Outline the Ames test
A test for DNA damage in which you use rat liver.
Homogenize rat liver and add test compound.
Metabolically activate the compound
Add to the salmonella HIS- on HIS- media
Count the number of colonies that are now on His+
What are the defences that protect DNA from attack by mutagens?
Physical shielding
Detoxification enzymes
DNA repair enzymes
What are the main families of DNA repair enzymes?
Mismatch repair enzymes
Methylguanine DNA methyltransferase (MGMT)
Base excision repair (BER)
Nucleoside excision repair (NER)
Outline mismatch repair
Mismatch repair, repairs incorrect base insertions
MSH2 and MSH3 flag base
Endonuclease 1 removes bases
RPA, PCNA< RFC, Pol delta or Pol epsilon replace excised DNA
What is the role of methylguanine DNA methyltransferases in DNA repair?
MGMT removes methyl or ethyl adducts from the O6 position of guanine by alkylating agents e.g. ENU
Give an example of a defect in a DNA repair gene which causes cancer
Familian Breast and Ovarian Cancer –> BRCA1
