Exam I - Carcinogenesis

Question 1

Carcinogenic factors

Answer 1

• diet
• exercise
• occupation
• sunlight
• smoking
• fat intake
• vegetable intake
• salt consumption
• EtOH consumption
• genes
• environment

Question 2

Oncogenes

Proto-oncogenes

Answer 2

-non-mutated oncogene

Question 3

Oncogenes

Purpose/Fxn

Answer 3

-promote cell growth/survival (mitogens)

Question 4

Oncogenes

What do they encode?

Answer 4

-Proteins in cell proliferation signaling pathway
(EGFR, K-ra, AKT, MAP Kinase)
-transription factors (c-myc)
-inhibitors of apoptosis (bcl-2)

Question 5

Tumor Suppressor Genes

Purpose/Fxn

Answer 5

• regulate cell cycle “check points”
• block tumor development
• programmed cell death (Bax)
• products sense DNA damage (p53, Rb)
• DNA repair (BRCA1/2

Question 6

Tumor Suppressor Genes

Inactivation Process

Answer 6

• requires homozygous inactive alleles
• one may be inherited, the other acquired (aka LOH)
• can be a 2nd hit mutation in a single cell

Question 7

Types of Carcinogens

Genotoxic/DNA Reactive

Answer 7

• most are chemical

- radiation, oxygen radicals, food, metabolic by-products

Question 8

Types of Carcinogens
Genotoxic/DNA Reactive
Organic
PAHs

Answer 8

-polycyclic aromatic hydrocrabons (benzo[a]pyrene/BaP)
(from combustion, smoking)
-benzene (myelodysplastic syndrome)
-activated by metabolism
-tissue specific

Question 9

Types of Carcinogens
Genotoxic/DNA Reactive
Organic
Mycotoxins

Answer 9

• alfatoxin B1 (AFB1) from A. flavus
• on grains in Africa, China
• hepatocarcinogen
• HBV=HCC

Question 10

Types of Carcinogens
Genotoxic/DNA Reactive
Physical

Answer 10

• radiation
• asbestos
• heavy metals

Question 11

Procarcinogens

Metabolism

Answer 11

• P450 enzymes
• usually metab’d to stable metabolite
• less often metab’d to reactive carcinogenix metabolite

Question 12

Carcinogens

Biochemical impact

Answer 12

• form covalent bands with DNA
• altered H-bonding -> misreading of damaged base
  (e. g. guanine binding to thymine in transcription)

Question 13

Non-genotoxic carcinogens

Biochemical impact

Answer 13

• no DNA interaction
• impact cell growth, incr DNA synth
• inhibit repair/enzyme fxns (metals)
• alter chromatin modifications (Ni)
• alter signaling pathways
• induce inflammation
• impact seen only at high concentrations, chronic exposure

Question 14

Non-genotoxic carcinogens

BPA effects

Answer 14

-endocrine diruption: upregs estrogen signaling