8 Intro to carcinogenesis: why and how neoplasms occur Flashcards
neoplasm is a … ?
newly formed collection of cells resulting from abnormal cellular proliferation that persists after the initial stimulus is removed
Give 3 features of benign tumours
1. they are generally …
2. localised / not localised
3. …… perimeter
- self-contained
- localised
- have a well-defined
How do benign tumours grow from a central mass ?
slowly, expanding outward
When are benign tumors dangerous ?
when they compress surrounding tissues
What could a benign tumor near a blood vessel do ?
restrict the flow of blood
What could a benign tumor in the abdomen do ?
impair digestion
What could a benign tumor in the brain do ?
cause paralysis
malignant tumours are …
1. location ?
2. action on surrounding tissues ?
3. of adjacent cells their growth is …
- not self-contained
- doesn’t compress
- irregular invasion
Although malignant tumors may grow slowly what are they capable of ?
very rapid growth
What are malignant tumors NOT in location comparison to benign tumors ?
localised
Through metastasis what do malignant tumors do ?
they shed cells that travel through the bloodstream and infect tissues at other locations
What are malignant tumors capable of doing ? include a example
establish malignant growth in a different type of tissue e.g. breast cancer can spread to bone tissue
What can neoplasms be either of ?
benign or malignant
What are the characteristics of a benign neoplasm ?
- well cicrumscribed (has distinct boundaries)
- slow growing
- non-invasive
- closely resembles the tissue of origin
Give 2 examples of benign neoplasms that are medically important
- uterine fibroids
- meningioma
what are the most common benign tumors in women of childbearing age ?
uterine fibroids
What percentage of women are affected by uterine fibroids by age 50?
80-90%
What are some symptoms associated with uterine fibroids?
Pain, excessive menstrual bleeding, or infertility.
What is the most frequently reported primary CNS tumor?
Meningioma
What proportion of all CNS tumors do meningiomas account for?
Approximately 36%.
What are some potential complications of meningiomas despite being benign?
Potential neurological symptoms due to their location in the central nervous system.
How can uterine fibroids potentially cause infertility ?
by obstructing the fallopian tubes and impairing gamete transport
what is metastasis ?
the spread of cancer cells to locations distant from their original site
Aetiology of cancer is … ? what does this mean ?
multifactorial i.e. is caused by intrinsic & extrinsic factors
Give some examples of intrinsic factors
- heredity
- age
- gender
- sex
- family history
- genetic mutations
give some examples of extrinsic factors
- chemicals
- radiation
- infections
what factors and access to healthcare affect cancer outcomes ?
socioeconomic factors and unequal access
Give 4 examples of some chemical carcinogenic agents
- polycyclic aromatic hydrocarbons (PAHs)
- aromatic amines
- nitrosamines
- asbestos (although not chemical , a naturally occuring silicate)
about 30% of cancer deaths is due to the 5 leading behavioural/dietary risk factors, which are… ?
- high BMI
- low consumption fruit/ vegetables
- no physical exercise
- smoking
- alcohol
Extrinsic factors which contribute to cancer aetiology are classified into 3 groups … ?
- chemicals
- radiation
- infections
Give an example of polycyclic aromatic hydrogcarbons (PAHs)
benzopyrene
Give an example of a nitrosamine which is an industrial carcinogen used in the dye manufacturing process
2-napythylamine
Malignant neoplasms caused by the nitrosamine 2-napythylamine showed that…
1. delay ?
2. risk of ?
3. specificity ?
- There is a long delay between carcinogen exposure & onset of malignancy
- Risk of cancer depends on the total carcinogen dose
- Sometimes organ specificity for particular carcinogens
- most carcinogens enter the body in the form of ?
- before being converted to …. by ….?
- an example of one of these converted substances ?
- procarcinogens
- carcinogens, cellular machinery
- benzopyrene
What is benzopyrene ?
- a procarcinogen
- one of main carcinogenic agents in cigarettes
- What must benzopyrene first be oxidised by ?
- and further modified by …. to become …..
- this binds …. to DNA to form an ….. where it causes mutations
- P450-1A1
- other enzymes, benzopyrene diol epoxide
- covalently, adduct
Inital chemical carcinogens are ?
mutagens
promoter chemical carcinogens cause … ?
prolonged proliferation in target tissue
What does the Ames test show ?
initiators are mutagens
promoters cause prolonged proliferation in target tissues
Via what process does the mutant monoclonal collection of cells become fully malignant ?
progression
What are complete carcinogens ?
carcinogens that act as both the initiators and promoters
How much does ultraviolet (UV) light penetrate ?
not deeper than skin
Ionising radiation =
1. any form of radiation that has the ability to ….
2. 2 examples
- remove electrons from atoms and molecules
- x-rays, nuclear radiation
Nuclear radiation =
particles or …1… emitted from the nucleus during ..2…
- electromagnetic radiation
- radioactive decay
what does nuclear radiation include ?
- alpha particles
- beta particles
- gamma rays
How does radiation cause cancer apart from the fact that radiation can damage DNA directly and indirectly ?
- misrepairs by DNA repair proteins allow the mutation/ chromosomal rearrangement to persist
By producing free radicals what can radiation do to DNA ?
damage it directly or indirectly
How can radiation damage DNA indirectly ?
- generate free radicals
- produce secretable soluble factors that can affect distal non-irradiated cells
What’s the most important type of radiation type and why ?
ultraviolet
we are exposed to this type of radiation daily from sunlight - increased risk of skin cancer
main exposure to ionising radiation for most people is … ?
natural background radiation from radon which seeps from earth’s crust
5 ways DNA can be damaged ?
- cellular metabolism
- replication errors
- ionising radiation
- ultra violet light
- toxic chemical
3 methods of DNA damage response ?
- checkpoint activation
- DNA repair
- apoptosis
Carcinogenesis is a multistep process , what are the 3 steps ?
- initiation - progenitor cell irreversible genetic mutation
- promotion -
- progression
Initiation stage in carcinogenesis involves what?
irreversible genetic mutation in stem cell/progenitor cell
promotion stage in carcinogenesis involves what?
- clonal expansion of initiated cells within generalised hyperplasia
what is outgrowth of pre-malignant tumours ?
papillomas
progression stage in carcinogenesis involves what?
malignant conversion to invasive carcinoma
What is there often between exposure to a carcinogen and clinically- detectable neoplasia ?
a long interval (latency period)
Pre-malignant (benign) tumours that can progress to invasive, malignant carcinomas
Papilloma
What are papillomas ?
pre-malignant (benign) tumours that can ultimately progress (following the acquisition of additional mutations) to an invasive, malignant carcinoma
What have animal tests shown with initiators and promoters (both are chemical carcinogens) ?
Initiators must be given first followed by a second class of carcinogens called promoters
what is the cell cycle a regular sequence of ?
growth and division that cells undergo
What is Ames test designed to detect ?
whether a chemical can cause mutations in the DNA of an organism
Ames test includes exposure of what ?
auxotrophic his (histidine) bacterial strains of Salmonella typhimurium to potential mutagens
Some infections directly affect …. that control …
genes, cell growth
Some infections directly affect genes that control cell growth whilst other do indirectly.
By causing ..1.. injury where the resulting ..2.. acts either as a ….3.. for any pre-existing mutations or else ..4.. new mutations from DNA ….5…
- chronic tissue
- regeneration
- promoter
- causes
- replication errors
From HPV what are the direct carcinogens that act by doing what in infected host cells ?
HPV-16 & HPV-18
* sustaining cell proliferation and resistance to apoptosis
HPV-16 and HPV-18 are strongly associated with what carcinoma ?
cervical
what viral oncogenes do HPV-16 and HPV-18 express ?
E6 and E7
Integration of HPV DNA into the host (human) genome allows what ?
transcription of 2 oncoproteins (E6 and 37)
what’s the action of the viral oncogenes E6 and E7 ?
E6 inhibits numan TP53 function while E7 inhibits human RB1 (pRB) protein function
What do proto-oncogenes encode for ?
a range of proteins with a range of normal functions
