Carcinogenesis

Question 1

General mechanisms of carcinogenesis

Answer 1

1. Failure of DNA repair; 2. Failure of apopotosis; 3. failure of mitosis termination

Question 2

Failure of DNA repair?

Answer 2

i. Epoxides bind to DNA; use excision repair
ii. Dose defines the poison–more epoxides on the DNA, the higher chance there is of the excision repair to make a mistake
iii. Xeroderma pigmentosum
1) Autosomal recessive trait; ER mechs don’t work

Question 3

Failure of apoptosis

Answer 3

a. Mitosis vs apoptosis balance

b. Cancer cells have apoptosis signals turned off, and mitosis signal turned off

Question 4

failure to terminate mitosis (cell prolif)

Answer 4

a. Nongenotoxic xenos cause cancers by inhibiting apoptosis ands timulating mitosis

Question 5

3 stages of cancer development

Answer 5

initiation, promotion, progression

Question 6

what is initiation?

Answer 6

a. Irreversible
b. Critical metabolic gene (ATP synthase) may be knocked out which prevents initiation from happening, but nothing cell can do about stopping initiation
c. Protoncogenes
i. Genes that get activated to protooncogenes, then activated to cancer genes, oncogenes
1) Oncogenes stimulate cell proliferations
d. Tumor suppressor genes inactivated
i. E.g. p53

Question 7

what is promotion?

Answer 7

a. Can have initiation, but not end up with cancer–you need promotion (and progression)
b. Reversible
i. Certain xenos are promoters
c. E.g. lead is a promoter
i. Becomes involved in signalling pathways dealing with promotion

Question 8

what are some promoters?

Answer 8

d. Hormones
e. Caloric intake
f. Ethanol

Question 9

What is progression?

Answer 9

a. Benign growth to malignant growth
b. irreversible
c. Chromosomal changes
i. Chromosomal abberations
ii. Chromosomes linking together
iii. Become a different “cell”?
iv. Nubmer of chromos, morphology can change

Question 10

what are complete carcinogens?

Answer 10

a. Are initiators, promotors, and progressors

E.g. tobacco (cigarettes)

Question 11

what are the categories of carcinogens?

Answer 11

genotoxic; nongenotoxic; cocarcinogens; solid state carcinogens; metals

Question 12

nongenotoxic carcinogens

Answer 12

DDTs, PCBs; endogenous mitogens; xenos that cause sustained cell injury

Question 13

how do DDTs and PCBs cause cancer?

Answer 13

involved in stimulating mitosis and inhibiting apoptosis

Question 14

what are the endogenous mitogens that can causecancer?

Answer 14

growth factors; estrogens and androgens

Question 15

what xenos can cause cell injury?

Answer 15

chloroform; § Causes hepatotoxicity (liver necrosis)

§ The more cells that divide increases the probably of an incorrect mitotic event

Question 16

what are cocarcinogens?

Answer 16

Not carcinogenic but increase the effect of a carcinogen (potentiation)

Question 17

define neoplasia

Answer 17

new growth or autonomous growth of tissue

Question 18

define neoplasm

Answer 18

the lesion resulting from neoplasm

Question 19

define benign

Answer 19

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

Question 20

define malignant

Answer 20

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

Question 21

define metastases

Answer 21

secondary growths derived from a primary malignant neoplasm

Question 22

define tumors

Answer 22

lesions characterized by swelling or increase in size which may or may not be neoplastic

Question 23

define cancer

Answer 23

malignant neoplasm

Question 24

define carcinogen

Answer 24

a physical or chemical agent that causes neoplasia

Question 25

define genotoxic

Answer 25

carcinogens that interact with DNA resulting in mutation

Question 26

define nongenotoxic

Answer 26

carcinogens that modify gene expression but do not damage DNA

Question 27

what are examples of hormonal promoters?

Answer 27

i. Steroid hormones stimulate division of muscle cells
ii. Growth hormone
iii. Endocrine disrupting chemicals (EDCs)
1) Hormone mimics– present in plastics

Question 28

how is caloric intake a promoter?

Answer 28

i. More energy intake, more energy and building blocks for cancer to use to proliferate

Question 29

what kinds of cancer does ethanol promote

Answer 29

Promotes esophageal cancer, throat cancer

Question 30

what are procarcinogens?

Answer 30

xenos that must first be activated to become carcinogenic (e.g. become epoxidated)