Carcinogenesis Flashcards
(113 cards)
1
Q
abnormal cells with abnormal growth
A
Carcinogenesis
2
Q
Abnormal cell differentiation and growth
A
Carcinogenesis
3
Q
T/F: In all types of cancer, some of the body’s cells begin to divide without stopping and spread into surrounding tissues
A
True
4
Q
Characteristics of Cancer:
_______________ in growth signals
Insensitivity to ____________
Evasion of ____________
Limitless ____________ potential
Tissue ____________ and ____________
Sustained ____________
A
Self-sufficiency; antigrowth signals; apoptosis; replicative; invasion and metastasis; angiogenesis
5
Q
stages of carcinogenesis
A
- Initiation
- Proliferation
- Promotion
6
Q
In this stage - cancer is already triggered (irreversible)
A
Initiation stage
7
Q
proliferation happens in this stage
A
Promotion
8
Q
Promotion is __________ (reversible/ireversible)
A
Reversible
9
Q
stage where neoplasia happnes
A
Progression
10
Q
Abnormal tissue growth in mucosal surface of colon (most common), ear canal, cervix
A
BENIGN TUMORS/POLY
11
Q
Can Benign tumors/poly be removed?
A
Yes, they are not life threatening
12
Q
Can Benign tumors/poly become malignant?
A
Yes
13
Q
Non Cancerous cells
A
Benign turmors
14
Q
Benign tumors are found in
A
mucosal surface of colon (most common), ear canal, cervix
15
Q
types of malignant tumors
A
carcinoma
sarcoma
16
Q
epithelial origin
A
carcinoma
17
Q
superficial origin
A
carcinoma
18
Q
Most common. Cancer of the skin or organ lining e.g., liver or kidneys
A
carcinoma
19
Q
of mesenchymal origin
A
sarcoma
20
Q
liquid type
A
sarcoma
21
Q
connective tissues
A
sarcoma
22
Q
loosely packed and can travel to new positions (e.g. blood vessels)
A
sarcoma
23
Q
Cancer of connective tissue e.g., bones, muscles, cartilage, & blood vessels
A
sarcoma
24
Q
Blood cancers
A
Leukemia
Hodgkin or non-hodgkin lymphoma, multiple myeloma
25
Bone marrow CA
Leukemia
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CA of the immune system
Hodgkin or non-hodgkin lymphoma, multiple myeloma
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with presence of Reed-Sternberg cells
Hodgkin
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These are giant cells found in Hodgkin Lymphoma
Reed-Sternberg cells
29
Agents that causes change in the gene structure
Mutagens
30
Mutagens may result from misread DNA through __________ and __________,__________ or broken DNA stands
transitions; transversions; frame-shifting
31
alter transcription due to insertion/deletion leading to incorrect DNA sequence
Frame shifting
32
T/F: Frame shfiting may prodce malfunctioning cells
true
33
DIRECT-ACTING GENOTOXIC CARCINOGENS
Carbonium ions
Nitrenium Ions
Free radicals
Diazonium ions
Epoxides
Aziridinium ions
Episultonium ions
Strained lactones
Sulfonates
Halo ethers
Enals
34
T/F: The development of cancer following exposure to chemical
carcinogens is a relatively rare event because of a cell’s ability to recognize and repair DNA.
True
35
DNA Repair mechanism:
The DNA region containing the adduct is removed and a new patch of DNA is synthesized, using the opposite intact strand as a template. The new DNA segment is then spliced into the DNA molecule in place of the defective one. To be effective in restoring a cell to normal, repair of DNA must occur prior to cell division.
Cut-and-Patch by pol 1
36
According to Cut-and-Patch by pol 1, to be effective in restoring a cell to normal, repair of DNA must occur _____________ (before or after) cell division.
prior/before
37
In **Cut-and-Patch by pol 1**, the DNA region containing the adduct is __________ and a new patch of DNA is synthesized, using the ________________ as a template.
removed; opposite intact strand
38
Fragment translation by pol 1
nick translation by pol 1
39
Typically repairs chemically modified nucleobases
Base Excision or Mismatch Repair of Single-base Mispairs
40
Removes altered base in the Base Excision or Mismatch Repair of Single-base Mispairs DNA repair mechansim
DNA glycosylase
41
In Base Excision or Mismatch Repair of Single-base Mispairs DNA repair mechansim, _________ fills the gap created by DNA glycosylase
pol 1
42
Cut DNA near apurinic sites
Apurinic endonucleases
43
The cut by apurinic endonucleases is then extended by ____________, and the resulting gap is repaired by _____________ and ____________
exonucleases; DNA polymerase and ligase
44
In this repair mechanism, photolyase Binds T-T cyclobutane dimer → Individual pyrimidine bases
Photoreactivation Repair
45
In photoreactivation repair mechanism, photolyase binds to ____________ (________) resulting to an individual _________ bases
T-T cyclobutane dimer (Thymine-thymine); pyrimidine
46
The double-strand break on one chromosome is repaired using the information on the homologous, intact chromosome
Homologous Recombination
47
In Homologous Recombination, the ____________break on one chromosome is repaired using the information on the homologous, intact chromosome
double-strand
48
The predominant mechanism for double-stranded DNA repair
Nonhomologous End-joining Repair of DNA
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T/F: During Nonhomologous End-joining Repair of DNA, Several base pairs are lost at the joining point. This type of deletion may produce a possible mutagenic coding change
True
50
CHEMICAL MUTAGENS
Polycyclic Aromatic Hydrocarbons (PAHs)
Alkylating agents (Electrophilic)
Aromatic amines and amides (Dyes)
Butylated Hydroxyanisole (BHA), Butylated Hydroxytoluene (BHT)
51
example of Polycyclic Aromatic Hydrocarbons (PAHs)
Benzopyrene
52
found in charcoal-broiled foods, tobacco, diesel exhaust
Benzopyrene
53
Example of Alkylating agents (Electrophilic)
Nitrosamines (tocino/longganisa preservative)
Aflatoxin (nuts)
Alkyl sulfates
Cytotoxic Alkylating agents -
54
Butylated Hydroxyanisole (BHA), Butylated Hydroxytoluene (BHT) may be found in
hotdog, potato chips
55
PHYSICAL MUTAGENS
UVB radiation (Sun exposure)
Ionizing radiation (x and gamma rays)
56
Only _______ and _______ can penetrate the ozone layer
UVA; UVB
57
furochomarane that is used for psoriasis and vitiligo treatment and is photosensitizing
Soralem
58
Non genotoxic carcinogens includes chemicals that functions via:
1. _________ cytotoxicity → _________ DNA Mutations
2. _________-mediated
3. _________ perturbation
4. Induction of _________
5. Modulation/ Alteration of _________ status
6. _________
1. Sustained cytotoxicity → Spontaneous DNA Mutations
2. Receptor-mediated
3. Hormonal perturbation
4. Induction of oxidative stress
5. Modulation/ Alteration of methylation status
6. Immunosuppresion
59
example of Sustained cytotoxicity → Spontaneous DNA Mutations
Chloroform
60
these are Receptor-mediated chemicals
Constitutive Androstane Receptor (CAR)
Peroxisome proliferator–activated receptor alpha (PPARα)
Aryl hydrocarbon receptor (AhR) effects
61
Phenobarbital
Constitutive Androstane Receptor (CAR)
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Fibrates
Peroxisome proliferator–activated receptor alpha (PPARα):
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Polychlorinated
biphenyls
Aryl hydrocarbon receptor (AhR) effects
64
Biogenic amines
Hormonal perturbation
65
Steroids Hormones: Phytoestrogens (Bisphenol A), Diethylstilbestrol
Hormonal perturbation
66
Tamoxifen
Hormonal perturbation
67
Peptide hormones: Chemical induce decrease in T3/ T4 levels and/ or increase in
TSH levels
Hormonal perturbation
68
Phytoestrogens (Bisphenol A), Diethylstilbestrol
Steroid Hormones
69
Chemical induce decrease in T3/ T4 levels and/ or increase in
TSH levels
Peptide hormones
70
ROS formers [superoxide anion (O2-), hydroperoxyl radical (HO2), hydrogen peroxide (H2O2 ), and the hydroxyl radical (OH)]: Ethanol, Lindane, Dieldrin, Acrylonitrile
Induction of oxidative stress
71
[superoxide anion (O2-), hydroperoxyl radical (HO2), hydrogen peroxide (H2O2 )
ROS formers
72
Ethanol, Lindane, Dieldrin, Acrylonitrile
hydroxyl radical (OH)]
73
Choline deficiency
Modulation/ Alteration of methylation status
74
Phthalates, Atrazine
Immunosuppresion
75
Inorganic Carcinogens
Metals (As, Be, Cd, Cr, Ni, Pb
76
The carcinogenic manifestations of metals (inorganic carcinogens) vary and include increased risk for _____, _______, ________ tumors
skin, lung, liver
77
Other Factors Affecting Carcinogenesis
Genes
Viral infection (Oncogenic viruses)
Environmental factors
78
Gene has more than one allele
Genetic Polymorphism
79
Gene mutations:
Proto-oncogenes
Tumor-suppressor genes
80
Encodes a protein capable of transforming cells in culture or inducing cancer in animals
Proto-oncogenes
81
involved in cell signaling cascades
Proto-oncogenes
82
Retinoblastoma Gene (Rb1), Breast CA Gene 1 (BRCA1), Wilms Tumor Gene (WT-1), p16, p53
Tumor-suppressor genes:
83
Rb1
Disorder: ________
Neoplasm: ________
Retinoblastoma; small-cell lung carcinoma
84
p53
Disorder: ________
Neoplasm: ________
Li-Fraumeni syndrome
Breast, colon, lung cancers
85
BRCA1
Disorder: ________
Neoplasm: ________
Unknown; Breast Carcinoma
86
WT-1
Disorder: ________
Neoplasm: ________
Wilms tumor
Lung Cancer
87
p16
Disorder: ________
Neoplasm: ________
Unknown; melanoma
88
Retroviruses:_________________→Sarcoma
Rous Sarcoma Virus (RSV)
89
7 DNA Tumor Viruses
Simian virus 40 (SV40), Polyoma virus, Hepatitis B virus, Human Papilloma viruses (HPV) , adenoviruses, herpes viruses, and Poxviruses
90
Lifestyle, Poor diets or overnutrition
Environmental factors
91
Assessing Carcinogenicity of Chemicals: In vitro
Ames Test
Mouse Lymphoma Assay
Chinese Hamster Ovary Test
Syrian Hamster Embryo
C3H/10T1⁄2 Cell Line Transformation Assay
92
Salmonella typhimurium strains, deficient in DNA repair and unable to synthesize histidine, are treated with several doses of the test compound.
Ames Test
93
In the presence of a mutagenic chemical, the defective histidine gene can be mutated back to a functional state (back mutation), resulting in a restoration of bacterial growth in medium lacking histidine.
Ames Test
94
Used to determine whether a chemical is capable of inducing mutation in eukaryotic cells.
Mouse Lymphoma Assay
95
The ability of cells in culture to acquire resistance to trifluorothymidine (the result of forward mutation at the thymidine kinase locus) is quantified.
Mouse Lymphoma Assay
96
Commonly used to assess the potential mutagenicity of chemicals with the hypoxanthine–guanine phosphoribosyltransferase (HGPRT) gene as the endpoint
Chinese Hamster Ovary (CHO) Test
97
Diploid cell transformation assay, measures carcinogenic potential of xenobiotics by assessing transformed colonies based on morphological criterion.
Syrian Hamster Embryo (SHE)
98
Originally derived from fibroblasts taken from the prostate of a C3H mouse embryo
C3H/10T1⁄2 Cell Line Transformation Assay
99
Most frequently used endpoint (after exposure to carcinogen): Morphological transformation of mammalian cell fibroblasts in culture
C3H/10T1⁄2 Cell Line Transformation Assay
100
Assessing Carcinogenicity of Chemicals: In vivo
ransgenic rodent mutation assay systems
101
Take into account whole
animal processes such as ADME of chemicals and their metabolites.
Assessing Carcinogenicity of Chemicals: In vivo
102
Based on the genes of the lac operon
Transgenic rodent mutation assay systems
103
Transgenic rodent mutation assay systems
MutaMouse
Big Blue, and Pig-a Gene Mutation Assay
104
Primarily performed in rats and is based on the X-linked Pig-a gene (phosphatidylinositol N- acetylglucosaminyltransferase, subunit A), which is involved in the production of glycosylphosphatidylinositol (GPI) anchor proteins on the cell surface
Pig-a gene mutation assay
105
Currently, the assay is optimized for measuring the Pig-a mutant phenotype in peripheral blood erythrocytes by quantification of** CD59- negative reticulocytes **and **red blood cells.**
Pig-a gene mutation assay
106
PIG-A meaning
phosphatidylinositol N- acetylglucosaminyltransferase, subunit A
107
Pig-a gene mutation assay is based on the X-linked Pig-a gene (phosphatidylinositol N- acetylglucosaminyltransferase, subunit A), which is involved in the production of __________________ anchor proteins on the cell surface
glycosylphosphatidylinositol (GPI)
108
Pig-a gene mutation assay is optimized for measuring the Pig-a mutant phenotype in _______________ blood erythrocytes by quantification of _________ reticulocytes and red blood cells.
peripheral ; CD59- negative
109
Chronic Testing for Carcinogenicity: In vivo
Chronic (Two Year) Bioassay Two-year
110
In Chronic Bioassay Two-year, ___________ levels of a test chemical (up to the __________ tolerated dose) and a ___________ are administered to 50 males and 50 females (mice and rats), beginning at ____________ of age, continuing throughout their lifespan
2-3 dose; maximum; vehicle control; 8 weeks
111
During the study, food consumption and bodyweight gain are monitored and the animals are observed clinically on a regular basis; at necropsy, the tumor number, location, and diagnosis for each animal are thoroughly assessed
Chronic (Two Year) Bioassay Two-year
112
is a multistage process that involves initial mutational events followed by changes in gene expression leading to the selected clonal proliferation of the precancerous cell.
Cancer
113
appears to exhibit multiple characteristics including increased selective lesion growth (through sustained cell proliferation and/or resistance to apoptosis), the induction of angiogenesis, enabling replicative immortality, activation of factors that influence invasion and metastasis, evasion of normal growth suppression, modulation of energy metabolism, and the avoidance of attack by the immune system.
Neoplasia
