Carginogenesis Flashcards
top three factors that cause human carcinogens
diet
tobacco
infection
a subset of lesions of the disease
cancer
the autonomous growth of tissue with permanently altered genetic make-up
neoplasia
neoplasms can be ____ or _____
benign or malignant
mesemchymal neoplasia are called
sarcomas
epithelial neoplasias are called
carcinomas
four different causes for formation of neoplasms
chemical
mechanical
radiation
viral infections
three different stages of carginogenesis
initiation
promotion
progression
three things about initiation
irreversible mutation
suppression of DNA repair
permanent DNA damage
two things about promotion
stimulation of clonal expansion by tumor promoters
inhibition of apoptosis
two things about progression
further chromosomal damage possible
conversion of preneoplastic lesion to neoplasm
mechanisms of chemical carcinogenesis
some compounds directly genotoxic
activation through biotransformation
procarcinogen, proximate carcinogen, ultimate carcinogen
activation by free radicals
examples of chemical carcinogens
polynuclear aromatic hydrocarbons azo dyes aromatic amines aflatoxin metals
target molecule for carcinogenesis
DNA
mutagenesis involves three things
covalent binding
cell proliferation
DNA damage
nucleotide base with a highly nucleophilic nitrogen
guanine
can bind t guanine and adenine causing double strand breaks, binding to phosphate backbone
R-alkyl groups
when adjacent bases link instead of linking with bases of complementary strand
pyrimidine dimers
when a base is changed so the codon is now a stoping codon in the middle of a protein sequence
nonsense mutation
when a base is changed so the codon codes for a different amino acid than the original polypeptide
missense mutation
when a base gets deleted shifting all the codons
frameshift mutation
repairing DNA by replacing damaged DNA by cutting DNA near apurinic sites that are extended by exonucleases and repaired by DNA polymerase and ligase
mismatch repair
five non-genotoxic agents
cytotoxic chemicals receptor mediated hormonal altered DNA methylation oxidative stress
three receptors that can be activated and activate gens to produce proteins that disrupt cell division
CAR, PPAR, AhR
often found in tumor cells, few specific codons with specific mutation profiles
Ras oncogenes
three types of genetic targets
proto-oncogenes
oncogenes
tumor suppressor genes
functions of genetic targets
cellular growth
signal transduction
nuclear trancription
what type of alterations are enough to mess with genetic targets
point mutations
three characteristics of p53 gene and protein
tumor suppressor gene
TF for many genes, detects DNA damage
stops cell cycle and induces DNA repair or apoptosis
what microorganism is used in the ames test
a microbe that cannot synthesize histidine
mutagenic compound used in the ames test will…
revert the microbe from histidine negative to histidine positive so I will grow on media without histidine
limitations to the ames test
not all mutagens will revert the microbe back
legions characterized by expansive growth, frequency, exhibiting slow rates of proliferation that do not invade surrounding tissue or other organs
benign neoplasms
demonstrates invasive growth characteristics, capable of spreading not only thorugh the organ of origin but via metastasis to other organs
malignant neoplasms
agents that interact with DNA to damage or change its structure
genotoxic carcinogens
agents that do not directly interact with nuclear DNA
may change gene expression, modify normal cell function, bind to or modify cellular receptors and increase cell growth
nongenotixic carcinogens
genes encode a wide array of proteins that function to control cell growth and proliferation
proto-oncogenes
tumor suppressor genes
a gene encoding a protein that is capable of transforming cells in culture or inducing cancer in animals
oncogenes
