Pathology - Carcinogens Flashcards
Carcinogen
Agent that is able to damage DNA, resulting in a heritable, non lethal mutation that gives rise to neoplasia
types of carcinogens
Chemical, radiation, microbes
Steps in chemical carcinogenesis
Initiation, promotion, direct acting, indirect, metabolism, target DNA
Initiation & promotion
I: Permanent DNA damage, irreversible
P: promote proliferation of initiated cells, no effect on DNA, damage is reversible
Direct acting, indirect damage
D: no metabolic conversion to be carcinogenic
I: metabolic conversion to be carcinogenic (majority of damage)
What metabolizes carcinogens?
Cytochrome p450 enzymes
Genes that encode enzymes are highly polymorphic differ greatly
Influence ones susceptibility too a carcinogen
Example of chemical carcinogen
Aflatoxin B1
(Mutate in TP53)
Ionizing radiation
Alpha, beta, gamma, x-ray
Radiation vs irradiation
Radiation is the number of photons that are being emitted by a single source. Irradiation, on the other hand, is one where the radiation is falling on the surface is being calculated.
Host defenses against UV irradiation (3)
Cutaneous pigments absorb
Aromatic portions of amino & Nucleic acids absorb
Free radical scavengers minimize damage
Primary target of UV irradiation?
DNA in pyrimidine molecules
How mutations occur in pyrimidine molecules
Formation of pyrimidine dimmers, result from covalent cross linking of base pairs
How mutations occur with ionizing radiation
Translocation, direct single/double strand dna breaks
Example of microbial carcinogenesis
Retroviruses (FLV, BLV, ALV)
DNA viruses (bovine papilloma virus)
Mechanism of retroviruses
Insert viral genome into cellular DNA of host cell, promoters & enhancers control viral gene expression & nearby cellular host genes
Mechanisms of DNA viruses
Viral genes encode oncoproteins capable of transforming infected cells, interfere w proteins encoded by TSG
3 main outcomes of bovine leukemia virus
Persistent infection w no clinical sings
Persistent lymphocytosis
Lymphoma (common in adults)
Mechanisms of feline leukemia virus
Randomly inserts into genome, oronasal contact or urine
Manifestations of FLV
Anemia, neoplasia, Immunosuppression, IMD, reproductive issues, enteritis, CNS, stomatitis
Lymphoma, leukemia
Mechanism of Avian Leukosis virus
Inserts near c-myc
Fecal-oral/horizontal
B cell lymphoma
Mechanisms of Gallic herpesvirus
Integrates viral genome into telomeres of host chromosome, encodes. T cell proliferations (inflammation, lymphoma, neurotrophic)
Mechanisms of papilloma virus
Causes cutaneous papillomas, viral proteins prevent suprabasal cells from becoming postmitotic, viral proteins bind E2F preventing inhibition from Rb
Helicobacter in humans
Gastric adenocarcinoma
Lymphoma
H. Pylori
Helicobacter in ferrets
Gastric carcinoma
H. Mustelae
