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