Pathongenesis of Cancer Flashcards
main group of etiologic factors of cancers
random
hereditary
environment/lifestyle
2 step theory of pathogenesis
only when an “initiator” was introduced to mice followed by an extended period of exposure to a “promotor” did cancer develop
indicates initiators cause long lasting damage and promotors amplify that damage over time
initiation- caused by genetic mutations
promotion- non genetic amplifiers
ames test
bacteria are devised that have lost the capacity to synthesize histidine
bacteria will only grow in histidine containing medium unless the ability to make histidine is restored by a mutation
test of mutagenecity
procarcinogens
metabolzed into carcinogens in the liver but are not carcinogenic prior to that
ex. aflatoxin
factors that are important in development of cancer
varying dose and duration of exposure
differences in DNA repair capability
differences in susceptibiliy d/t polymorphisms
differences in immune function
differences in diet
how does radiation cause cancer
causes mutagenic oxidative free radicals leading to DNA damage and chromosomal breakage
properties of transformed cells
foci of transformed cells are clonal outgrowths
altered morphology
ability to proliferate indefinitely
loss of contact inhibition
reduced requirement for growth factors
increased intracellular transport of glucose
tumorgenecity
RNA and DNA viruses integrate their genes into the host genome to cause cancer
ok
RSV
RNA virus that gives cancer to chickens
genes include: gag pol and env
v src- has transforming capacity and was called an oncogene
major mechanisms of cancer associated genome instabililty
classes of genes that are deregulated:
proto-oncogenes
tumor suppressor genes
genes regulating apoptosis
DNA repair genes
types of genetic dysregulation
mutations
chromosomal rearrangements, deletions, and aneuploidy
gene amplification
epigenetic changes
DNA repair mechanisms
excisional repair of UV induced thymine dimers
DNA mismatch repair
homologous recombination repair
characteristics that allow for hallmarks of cancer
genome instability
tumor promoting inflammation
permissive cues from altered stromal microenvironment
hallmarks of cancer
sustained proliferative signaling- production of growth factors by tumor or tumor associated stroma, activation of downstream growth factor receptors, or disruption of signals that attenuate growth
evasion of growth suppressors
invasion and metastases- loss of adherence to other cells, conversion to fibroblast like morphology, increased motility, and expression of matrix degrading enzymes
