L21: Mechanisms Of Oncogenesis Flashcards
What is cancer characterised by?
→Abnormal cell proliferation
→ Tumour formation
→Invasion of neighbouring normal tissue
→Metastasis to form new tumours at distant sites
What are the two enabling characteristics of cancer?
→genome instability
→tumour inflammation
What are the two emerging hallmarks of cancer?
→avoiding immune destruction
→ reprogramming energy metabolism
What are the hallmarks of cancer?
→sustaining proliferative signalling →resisting cell death →genome instability →enabling replicative immortality →evading growth suppressors
How has long life span increased risk of cancers?
→longer we live the more time there is for DNA to accumulate
mutations that may lead to cancer
What type of developmental is cancer?
→clonal
How does heterogeneity arise in tumour cells?
→Tumour cells can ‘evolve’- sub clonal selection allowing a growth advantage
→Dependent on interaction with other tumour cells and the tumour microenvironment
What are proto-oncogenes?
→Normal genes that can be activated to be oncogenic
What is an oncogene?
→a proto-oncogene that has been mutated in a way that leads to signals that cause uncontrolled growth
What are tumour suppressor genes?
→inhibit both growth and tumour formation
→braking signals during phase G1 of the cell cycle, to stop
or slow the cell cycle before S phase.
What are the 3 assumptions in multistage carcinogenesis?
→Malignant transformation of a single cell is sufficient to give rise to a tumour
→Any cell in a tissue is as likely to be transformed as any other of the same type
→Once a malignant cell is generated the mean time to tumour detection is generally constant
What are the five models of carcinogenesis?
→mutational →genome instability →non-genotoxic →Darwinian →tissue organisation
What supports that cancer arises through the accumulation of irreversible DNA damage?
→presence of multiple mutations in critical genes is a distinctive feature of cancer cells
What are the 4 classes of carcinogens?
→chemical
→physical
→heritable
→viral
What are the two types of physical carcinogens?
→radiation eg ionisation or ultraviolet
→asbestos
What are two examples of viral carcinogens?
→Hepatitis B
→Epstein Barr
How do chemical carcinogens exert their effects?
→effects by adding functional groups to DNA bases called DNA adducts
Give an example of a chemical carcinogens
→coal tar, which contains benzo[a]pyrene, a polycyclic hydrocarbon
What chemical carcinogen is easiest to enter cells?
→Benzo[a]pyrene
Which enzymes in the body activate benzopyrene?
→cytochrome p450
What is the function of Ames test?
→determine the mutagenic activity of chemicals by observing whether they cause mutations in sample bacteria
How does the Ames test work?
Point mutations are made in the histidine (Salmonella typhimurium) or the tryptophan (Escherichia coli) operon,
→the bacteria incapable of producing the corresponding amino acid
→organisms that cannot grow unless histidine or tryptophan is supplied.
→culturing His-Salmonellais in a media containing certain chemicals, causes mutation in histidine encoding gene, such that they regain the ability to synthesize histidine
how do physical carcinogens exert their effects?
→imparting energy into the biological material
→DNA breaks Pyrimidine dimers
→Translocations
Mutations as a result of failed repair
What type of mutations are found in hereditary malignant syndromes?
→mutation of a single gene
