Pathology: Carcinogens

Question 1

What are carcinogens?

Answer 1

an agent that is able to damage DNA, resulting in a heritable, nonlethal, mutation that gives rise to neoplasia

Question 2

What are the three types of carcinogens?

Answer 2

Chemical
Radiation
Microbes

Question 3

What is an important concept to keep in mind about DNA damage and neoplasia?

Answer 3

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

Question 4

What do you need both of to cause tumor growth?

Answer 4

Initiation and Promotion

Question 5

What are the characteristics of chemical carcinogen initiation?

Answer 5

permanent DNA damage
irreversible

Question 6

What are the characteristics of chemical carcinogen promotion?

Answer 6

promote proliferation of initiated cells
no effect on DNA
reversible

Question 7

What are the differences between direct acting and indirect acting chemical carcinogens?

Answer 7

Direct require no metabolic conversion to be carcinogenic
Indirect require metabolic conversion to be carcinogenic

Question 8

what are most carcinogens metabolized by?

Answer 8

Cytochrome P450 enzymes

Question 9

What is important about genes that encode Cytochrome P450 enzymes?

Answer 9

The genes that encode Cytochrome P450 enzymes are highly polymorphic so differ greatly between individuals

Question 10

What is the relationship between Alphatoxin B1, hepatocellular carcinoma and TP53?

Answer 10

Individuals that ingest alphatoxin B1 at high levels predominantly end of with hepatocellular carcinoma due to a mutation in TP53

Question 11

what types of radiation causes neoplastic transformation?

Answer 11

ultraviolet radiation
Ionizing radiation (alpha, beta, gamma, and x-ray)

Question 12

What are the normal host defenses against UC radiation?

Answer 12

Cutaneous pigments (melanin) absorb irradiation
aromatic portions of amino & nucleic acids also absorb irradiation
free radical scavengers minimize damage

Question 13

What is the primary target of UV irradiation in DNA?

Answer 13

Pyrimidine molecules

Question 14

How are mutations formed due to UV irradiation in DNA?

Answer 14

photon of light is absorbed by DNA thus formation of pyrimidine dimers which forms mutations

Question 15

What do Pyrimidine dimers result from?

Answer 15

The crosslinking of base pairs

Question 16

How are mutation formed due to free radical-mediated DNA damage?

Answer 16

Translocation, direct signal/double strand breaks

Question 17

What is the primary microbe responsible for microbial carcinogenesis?

Answer 17

Viruses

Question 18

What are the characteristics of oncogenic retroviruses?

Answer 18

Insert viral genome into cellular DNA of host

Question 19

What are examples of oncogenic retroviruses?

Answer 19

Feline leukemia virus, bovine leukemia virus, avain leukosis virus

Question 20

What are the characteristics of oncogenic DNA viruses?

Answer 20

Viral gene encode oncoproteins capable of transforming infected cells

Question 21

How do oncogenic retroviruses cause neoplasia

Answer 21

promotors & enhancers control viral gene expression & nearby cells host genes, especially important when inserted near a proto-oncogene

Question 22

How do oncogenic DNA viruses cause neoplasia?

Answer 22

often interfere with the proteins encoded by tumor suppressor genes

Question 23

What is an example of oncogenic DNA viruses?

Answer 23

Bovine papillomavirus

Question 24

How is Bovine Leukemia virus inserted into the host genome?

Answer 24

It is inserted randomly into the genome

Question 25

How are cattle infected with bovine leukemia virus?

Answer 25

infected through transfer of blood & blood by products containing infected lymphocytes

Question 26

What are the 3 outcomes of Bovine leukemia virus?

Answer 26

1) persistent infection with no clinical signs 2) persistent lymphocytosis 3)Lymphoma: most common in adult cattle

Question 27

How is Feline Leukemia virus inserted into the host genome?

Answer 27

It is inserted randomly into the genome

Question 28

How are cats infected with feline leukemia virus?

Answer 28

oronasal contact with infectious saliva or urine, in uteros through nursing is also common

Question 29

What are the possible manifestations of feline leukemia virus?

Answer 29

Anemia, neoplasia, immunosuppression, immunemediated, diseases, reproduction problems, enteritis, neurologic dysfunction & stomatitis, and lymphoma and leukemia

Question 30

How is Avian Leukosis virus inserted into the host genome?

Answer 30

inserted near c-myc

Question 31

How are birds infected with avian leukosis virus?

Answer 31

fecal-oral transmission & horizontal transmission

Question 32

How are birds infected with avian leukosis virus?

Answer 32

fecal-oral transmission & horizontal transmission

Question 33

What are the possible manifestations of avian leukosis virus?

Answer 33

B cell lymphoma

Question 34

How is Gallid Herpesvirus-2 inserted into the host genome?

Answer 34

integrate its viral genome into the telomeres of host chromosomes & encodes a telomerase

Question 35

How is Gallis Herpesvirus-2 spread?

Answer 35

highly contagious through dander in the environment

Question 35

How is Gallis Herpesvirus-2 spread?

Answer 35

highly contagious through dander in the environment

Question 36

What are the possible manifestations of Gallid Herpesvirus-2?

Answer 36

T cell proliferations: inflammation, lymphoma, neurotropic

Question 37

What species do papillomaviruses infect?

Answer 37

horses, dogs, cattle & others

Question 38

What age of animal are preferentially affected by papillomaviruses?

Answer 38

Young animals

Question 39

What does the persistence of papillomaviruses suggest?

Answer 39

Immune dysregulation

Question 40

How do papillomaviruses have marked epidermal thickening?

Answer 40

viral proteins prevent suprabasal cells from becoming postmitotic and viral protein binds E2F preventing inhibition from Rb

Question 41

What does Helicobacter cause in humans?

Answer 41

Gastric adenocarcinoma Lymphoma H. pylori

Question 42

What does Helicobacter cause in ferrets?

Answer 42

Gastric carcinoma H. mustelae

Question 43

What is the likely mechanism of Helicobacter?

Answer 43

chromic G.I inflammation & attempts @ repair