15. Neoplasia 3 Flashcards
What are the intrinsic carcinogens?
Heredity - usually cancers in younger people
Age - older due to constant accumulation of somatic mutations
Sex - particularly hormones
What are the extrinsic carcinogens?
Environment - chemicals, radiation, infection
Behaviour - smoking, drinking
How can 4 in 10 cases of cancer be prevented?
Not smoking Maintain a healthy weight Sun safety Healthy balanced diet Cut back on alcohol Being active
What lessons can chemicals teach about carcinogenesis?
There is a long delay between carcinogen exposure and malignant neoplasm onset
Risk of cancer depends on total carcinogen dosage
There is sometimes organ specificity for particular carcinogens
What does chemical carcinogenesis involve?
Initiation and promotion
Sequence in which carcinogens are administered is critical
Imitators must be given first
Followed by a second class of carcinogens called promotors
What needs to happen to pro-carcinogen?
Activated in liver by cytochrome p450 into carcinogen
What is a complete carcinogen?
Chemical that is both an initiator and promoter
Name 2 complete carcinogens
Asbestos
Cigarette smoke
How can radiation damage DNA directly?
Causes missense mutations and double stranded DNA breaks
How does radiation cause damage?
Can damage DNA directly by mutations or indirectly by generating free radicals
How do infections act as carcinogens?
Some infections directly affect genes that control cell growth
Others do so indirectly by causing chronic tissue injury and the resulting regeneration acts either a a promoter for pre-existing mutation or causes new mutations from DNA replication errors
Which infections have direct effects?
HPV
Which infections have indirect effects?
Hep B virus as causes chronic tissue injury and inflammation so is a promoter
How does the human papilloma virus work?
Makes 2 proteins E6 and E7
Virus infects cell, ensures it doesn’t die then hijacks DNA replication machinery to make more virus particles
E6 inhibits p53 which prevents cell from undergoing apoptosis
Hijacks cell cycle by interfering with retinoblastoma protein which is important as a cell cycle checkpoint
Describe the RAS pathway when a point mutation has occurred
Growth factor binds to receptor
Causes conformational change of protein, activating RAS, in point mutation RAS is permanently activated
Causes cyclin D to upregulate CDK and phosphorylates
In point mutation, permanently allows cells to enter cell cycle and proliferate
What can proto-oncogenes encode?
Growth factors Growth factor receptors Plasma membrane signal transducers Intracellular kinases Transcription factors Cell cycle regulators and apoptosis regulators
What is the relationship between proto-oncogenes and tumour suppressor genes?
Play opposing roles in cel signalling pathway
What is xeroderma pigmentosa?
Autosomal recessive disease
Due to mutations in one of 7 genes that affect DNA nucleotide
Very sensitive to UV damage and develop skin cancer at a young age
What is hereditary non-polyposis colon cancer syndrome?
Autosomal dominant
Associated with colon cancer
Germ line mutations affects one of several DNA mismatch repair genes
What is familial breast carcinoma?
BRCA1/BRCA2 genes
Involved in repairing double strand DNA breaks
Can also be found in sporadic malignant neoplasms
If not present or overactive, cannot repair DNA therefore develop cancer
What are the hallmarks of cancer?
Self sufficiency in growth signals Resistance to growth stop signals Cell immortalisation Sustained ability to induce new blood vessels Resistance to apoptosis Ability to invade and produce metastases
