Pathology: Carcinogens Flashcards
What are carcinogens?
an agent that is able to damage DNA, resulting in a heritable, nonlethal, mutation that gives rise to neoplasia
What are the three types of carcinogens?
Chemical
Radiation
Microbes
What is an important concept to keep in mind about DNA damage and neoplasia?
Severely damaged DNA will not replicate, thus toxic agents may have the potential to induce tumors, but @ high concentrations damage & kill cells before this effect is expressed
What do you need both of to cause tumor growth?
Initiation and Promotion
What are the characteristics of chemical carcinogen initiation?
permanent DNA damage
irreversible
What are the characteristics of chemical carcinogen promotion?
promote proliferation of initiated cells
no effect on DNA
reversible
What are the differences between direct acting and indirect acting chemical carcinogens?
Direct require no metabolic conversion to be carcinogenic
Indirect require metabolic conversion to be carcinogenic
what are most carcinogens metabolized by?
Cytochrome P450 enzymes
What is important about genes that encode Cytochrome P450 enzymes?
The genes that encode Cytochrome P450 enzymes are highly polymorphic so differ greatly between individuals
What is the relationship between Alphatoxin B1, hepatocellular carcinoma and TP53?
Individuals that ingest alphatoxin B1 at high levels predominantly end of with hepatocellular carcinoma due to a mutation in TP53
what types of radiation causes neoplastic transformation?
ultraviolet radiation
Ionizing radiation (alpha, beta, gamma, and x-ray)
What are the normal host defenses against UC radiation?
Cutaneous pigments (melanin) absorb irradiation
aromatic portions of amino & nucleic acids also absorb irradiation
free radical scavengers minimize damage
What is the primary target of UV irradiation in DNA?
Pyrimidine molecules
How are mutations formed due to UV irradiation in DNA?
photon of light is absorbed by DNA thus formation of pyrimidine dimers which forms mutations
What do Pyrimidine dimers result from?
The crosslinking of base pairs
How are mutation formed due to free radical-mediated DNA damage?
Translocation, direct signal/double strand breaks
What is the primary microbe responsible for microbial carcinogenesis?
Viruses
What are the characteristics of oncogenic retroviruses?
Insert viral genome into cellular DNA of host
What are examples of oncogenic retroviruses?
Feline leukemia virus, bovine leukemia virus, avain leukosis virus
What are the characteristics of oncogenic DNA viruses?
Viral gene encode oncoproteins capable of transforming infected cells
How do oncogenic retroviruses cause neoplasia
promotors & enhancers control viral gene expression & nearby cells host genes, especially important when inserted near a proto-oncogene
How do oncogenic DNA viruses cause neoplasia?
often interfere with the proteins encoded by tumor suppressor genes
What is an example of oncogenic DNA viruses?
Bovine papillomavirus
How is Bovine Leukemia virus inserted into the host genome?
It is inserted randomly into the genome
How are cattle infected with bovine leukemia virus?
infected through transfer of blood & blood by products containing infected lymphocytes
What are the 3 outcomes of Bovine leukemia virus?
1) persistent infection with no clinical signs
2) persistent lymphocytosis
3)Lymphoma: most common in adult cattle
How is Feline Leukemia virus inserted into the host genome?
It is inserted randomly into the genome
How are cats infected with feline leukemia virus?
oronasal contact with infectious saliva or urine, in uteros through nursing is also common
What are the possible manifestations of feline leukemia virus?
Anemia, neoplasia, immunosuppression, immunemediated, diseases, reproduction problems, enteritis, neurologic dysfunction & stomatitis, and lymphoma and leukemia
How is Avian Leukosis virus inserted into the host genome?
inserted near c-myc
How are birds infected with avian leukosis virus?
fecal-oral transmission & horizontal transmission
How are birds infected with avian leukosis virus?
fecal-oral transmission & horizontal transmission
What are the possible manifestations of avian leukosis virus?
B cell lymphoma
How is Gallid Herpesvirus-2 inserted into the host genome?
integrate its viral genome into the telomeres of host chromosomes & encodes a telomerase
How is Gallis Herpesvirus-2 spread?
highly contagious through dander in the environment
How is Gallis Herpesvirus-2 spread?
highly contagious through dander in the environment
What are the possible manifestations of Gallid Herpesvirus-2?
T cell proliferations: inflammation, lymphoma, neurotropic
What species do papillomaviruses infect?
horses, dogs, cattle & others
What age of animal are preferentially affected by papillomaviruses?
Young animals
What does the persistence of papillomaviruses suggest?
Immune dysregulation
How do papillomaviruses have marked epidermal thickening?
viral proteins prevent suprabasal cells from becoming postmitotic and viral protein binds E2F preventing inhibition from Rb
What does Helicobacter cause in humans?
Gastric adenocarcinoma
Lymphoma
H. pylori
What does Helicobacter cause in ferrets?
Gastric carcinoma
H. mustelae
What is the likely mechanism of Helicobacter?
chromic G.I inflammation & attempts @ repair
