Carcinogenesis lecture:

Question 1

Proto-oncogenes are involved in regulationof what?

Answer 1

cell proliferation (mitosis)

Question 2

Define promotion, is it reversible or irreversible?

Answer 2

Initiated cells that dividing like crazy and forms a focal lesion. Promotion is reversible!

Question 3

Tumor:

Answer 3

Lesion characterized by swelling or increase in size, may or may not be neoplastic

Question 4

Metastases:

Answer 4

Secondary growths derived from a primary malignant neoplasm

Question 5

what are 4 examples of metals that are carcinogens?

Answer 5

1. Arsenic
2. Nickels
3. Chromium
4. Cadmium

Question 6

define progression, is it reversible or irreversible?

Answer 6

Progression of this focal lesion to this malignant neoplasia/tumor. Extremely evil cells that lots of weird stuff happens. This is irreversible

Question 7

Neoplasia:

Answer 7

new growth or autonomous growth of tissue

Question 8

Cancer:

Answer 8

Malignant neoplasm

Question 9

Nongenotixic:

Answer 9

Carcinogens that modify gene expression but do not damage DNA

Question 10

Define group 2b: Evidence for group 2b:

Answer 10

Agent is possibly carcinogenic to humans

Human epidemiological data is weak Animal data positive

Question 11

what are the 5 categories of carcinogens?

Answer 11

1. Genotoxic carcinogens
2. Non-genotoxic carcinogens (epigenetics)
3. Cocarcinogens
4. Solid state carcinogens
5. Metals

Question 12

Benign:

Answer 12

Lesions characterized by expansive growth, frequently exhibiting slow rates of proliferation that do not invade surrounding tissues

Question 13

Carcinogen:

Answer 13

A physical or chemical agent that causes or induces neoplasia

Question 14

define complete carcinogens: and provide an example.

Answer 14

involved in all three stages! Initiation, promotion and progression! ex.) tobacco smoke

Question 15

Describe the happy and sad pathways of this image:

Answer 15

The bioactivation is what makes those silly epoxides.

:): this reactive metabolite can interact wityh GSH and detoxify it!

:(: The ultimate carcinogen binds with DNA and causes alteration with that DNA which is now called bulky DNA.

:): This bulky DNA can be repaired by nuceltoide excision repair

:(: but if it was to continue on and that mutation is retained genetically, this really sucks when it activated the tumor supressor genes or proto-oncogenes

Question 16

what is an example of a tumor suppressor gene mutation that results in about half of human cancers?

Answer 16

p53

Question 17

Define group 3: Evidence for group 3:

Answer 17

Agent is not classifiable as to carcinogenicity to humans. Human and animal data inadequate

Question 18

what is Aflatoxin B1-

Answer 18

fungal metabolite in improperly stores foods. Used to study carcinogenesis because we know they cause cancer. Also an example of a procarcinogen tirned into an ultimate carcinogen

Question 19

Define group 4: Evidence for group 4:

Answer 19

Agent is probably not carcinogenic to humans Human and animal data negative

Question 20

give an example of a procarcinogen turned into ultimate carcinogen:

Answer 20

PAHs (polycyclic aromatic hydrocarbons)- Can be activated by CYP to produce this epoxide. Irreversible effects so you need DNA repair to clip it out. When you damage a specific portion of the DNA like the pronco-oncogenes or tumor suppressor genes thats when cancer occurs.

Question 21

Neoplasm:

Answer 21

the lesion resulting from the neoplasia

Question 22

what are the malfunctions of various repair/protective processes that can result in cancer:

Answer 22

1. Failure of DNA repair 2. Failure of apoptosis 3. Failure to terminate cell proliferation

Question 23

describe solid state carcinogens and give 2 examples?

Answer 23

Does not interact with DNA but there is constant irritation. Fine particles in alveoli just cause constant irritation and stimulate proliferation and you end up with a rare form of cancer.

ex.) asbestos, silica

Question 24

is initiation reversible or irreversible?

Answer 24

irreversible

Question 25

Describe genotoxic carcinogens?

Answer 25

Most concering, this produces metabolites that can damage DNA and if that region of DNA is related to proto-oncogenes or tumor supressor genes, that is what leads to at least half of all human cancers!

Question 26

how many types of cancer are there?

Answer 26

\>200

Question 27

what are the 3 distinct stages of carcinogenesis:

Answer 27

1. Initiaion 2. Promotion 3. Progression

Question 28

define non-genotoxic (epigenetic) carcinogens:

Answer 28

stimulators of mitosis and/or inhibitors of apoptosis. But it does not damage DNA.

Question 29

2 examples of cocarcinogens?

Answer 29

ethanol and asbestos

Question 30

Cancer is a complex. -------------- disease

Answer 30

multifactorial

Question 31

define procarcinogens and ultimate carcinogens:

Answer 31

Although some xenobitoics are direct-acting , most carcinogenic chemicals are inactive (called procarcinogens) and must be bioactivated to yield reactive metabolites such as epoxides (called ultimate carcinogens)

Question 32

whats the role of P53?

Answer 32

In normal cells, the damage can be repaired or the cell is pushed into apoptosis. However, in cells with mutatedt P53, reuslting in lack of p53 function, this control mechanism is no longer operating and the cell undergoes uncontrolled proliferation.

Question 33

Define group 1: Evidence for group 1:

Answer 33

Agent is carcinogenic to humans Human data is strong Animal data is strong

Question 34

what are 4 examples of promoters?

Answer 34

1. Xenobitoics 2. Hormones 3. Caloric intake 4. Ethanol

Question 35

Genotoxic:

Answer 35

Carcinogens that interact with DNA resulting in mutation

Question 36

Evidence for cancer-causing chemicals comes from 2 places, what are they?

Answer 36

1. Human data (usually epidemiological) 2. Lab animals (dose-response experiments)

Question 37

define co-carcinogens?

Answer 37

Not carcinogenic but increase effect of carcinoens. It potentiates the effect of a carcinogen. Mainly involved in ADME.

Question 38

Malignant:

Answer 38

Lesions demonstrating invasive growth, capable of metastases to other tissues and organs

Question 39

Tumor supressor genes are playfully termed what?

Answer 39

guardians of the genome

Question 40

describe 2 examples of non-genotoxic (epigenetic) carcinogens?

Answer 40

DDT- mitogens Endogenous mitogens- hormones, growth factors

Question 41

Define group 2a: Evidence for group 2a:

Answer 41

Agent is probably carcinogenic to humans Human epidemiology data suggestive Animal data positive

Question 42

what are the two ways in which initiation can occur?

Answer 42

1. Neoplasia- proto-oncogenes --\> oncogenes. This occurs through a mutations and that mutations is caused through DNA damage 2. Tumor suppressor genes- these are cells that initiate cells to die. They get mutated as well and fail to stop mitosis.