Topic 10: Cancer 2 Flashcards
what are the different type of carcinogens and how
- direct: must get inside the body
- indirect: get activated by metabolic process of liver
how do carcinogens induce cancer?
they manipulate the DNA of the cell
example of direct acting carcinogens
ethyl methanesulfonate: changes the sugar of the deoxyribonucleotide so the base pair is not boned to its correct pair (point mutation)
example of indirect carcinogen
Aflatoxin (from aspergillus flavus) gets converted into aflatoxin-2,3-epioxide by the cytochrome P-450
what is the difference between a direct and indirect acting carcinogen
indirect carinogens gets converted in the liver by an enzyme called cytochrome P450 changing them form water insoluble, unreactive to reactive and soluble then they get excreted into the blood stream allowing them to bind to DNA impairing it
how can viruses cause cancer?
DNA viruses can encode their DNA into the DNA of a cell which causes mutations and increases cell proliferation so the virus can multiply
examples of virus causing cancer
- HPV (human papillomavirus) encodes in dna and increases cell proliferation
- HIV leads to immunodeficiency preventing immune system from getting rid of some cancers
what is the genetic basis of cancer
there are some genes that there alterations frequently cause cancer called cancer critical genes
three classes
- proto-oncogenes
- tumor supressors
- caretaker genes (DNA maintenance)
what is the difference between an Onco gene and proto-oncogene
a proto oncogene is a normal gene that is usually involved in cell proliferation
- if mutated turns into a oncogene as it will cause over expression or activation (gain a function)
what is mutated in 30% of cancers and what does it cause?
RAS and its a point mutation that causes all RAS to NOT hydrolyze GTP (which means it stays on)
what do src genes do in viral & mammalian geomones
it is a cellular gene (c-src) that has picked up a retrovirus that causes sarcomas (now v-src) by inducing signal transduction pathways that drive cell proliferation.
what are the different ways a proto oncogene can turn into a oncogene
- constitutive activation of intracellular signal transduction proteins
- mutations in an RTK that results in independent activity
- constitutive activation of intracellular signal transduction through chromosomal translocation
explain how constitutive activation of intracellular signal transduction proteins can turn a proto-oncogene into a oncogene (src example)
- in c-src, a phosphorlayted Try 527 (P-Try 527) binds to the SH2 domain causing a conformational change in the kinase domain so it is inactive
- if Try-527 is deleted or mutated, the kinase will stay on (constitutive kinase activity)
what is another example of how constitutive activation of intracellular signal transduction proteins can turn a proto-oncogene into a oncogene
the mutation of Ras as it leads to the constitutive activation of MAPK
explain mutations in an RTK that results in independent activity can turn a proto-oncogene into a oncogene
a point mutation can lead to the dimerization without any signal so the receptor stays on
explain how constitutive activation of intracellaur signal transduction through chromosomal translocation can turn a proto-oncogene into a oncogene (abl example)
the ABL (a cytosolic protein kinase) and BCR gene get translocated fusing together mutating its function of promoting branching of actin control the cytoskeleton and shape of a cell
- if it occurs in a hematopoietic then white blood cells start expanding and its called CML (chronic myelongeous leukaemia)
what is the function of a cytokine
signalling molecules for inflammation due to tissue damage or infections
how can drugs block the effect of an oncogene at different stages of the respective signalling pathways
since BCR-ABL can phosphorylate JAK and STAT the signalling pathway for cytokines when cytokines aren’t actually present, drugs like imatinb (Gleevec) can block the ATP binding pocket oF BCR-ABL so it can’t phosphorylate them anymore
how can cytotoxic T cells kill a cancer cell?
some cancers causes changes in the amino acids of the cell to make a tumor neoantigen that gets detected by T cells to kill it.
what are immune checkpoint inhibitors?
PDL1/PDL: they stop the inhibition of antigen recognizing T lymphocytes but it usually doesn’t work in patients
