Chemical Carcinogenesis Flashcards
1
Q
Abnormal cell differentiation and growth
A
Cancer/Neoplasm
2
Q
In all types of cancer, some of the body’s cells begin to ______ without stopping and ______ into surrounding tissues
A
Divide; spread
3
Q
1 cm tumor (~1g) = _______ cancer cells
A
1 billion (10⁹)
4
Q
1 kg = ______ cancer cells
A
10¹² (1 trillion)
5
Q
Characteristics of Cancer:
- __________ in growth signals
- __________ to antigrowth signals
- __________ of apoptosis
- Limitless __________ potential
- Tissue _________ and _________
- Sustained ___________
A
- Self-sufficiency
- Insensitivity
- Evasion
- Replicative
- Invasion; metastasis
- Angiogenesis
6
Q
One of the characteristics of cancer is the spread outside of its original location. What is that term?
A
Metastasis
7
Q
In cancer, there is formation of new blood vessels. What is that term?
A
Angiogenesis
8
Q
Reversible stage of carcinogenesis by stopping the tumor promoter of the one responsible of spreading the damaged cells but only until initiation
A
Promotion
9
Q
Triggered by tumor promoter
A
Initiated cell
10
Q
The first stage of carcinogenesis
A
Initiation
11
Q
Irreversible stages of carcinogenesis
A
Initiation and progression
12
Q
Abnormal tissue growth in mucosal surface of colon (most common), ear canal, cervix.
A
Benign Tumors / Polyp
13
Q
Malignant tumor of epithelial origin
A
Carcinoma
14
Q
Most common. Cancer of the skin or organ lining e.g., liver or kidneys
A
Carcinoma
15
Q
Malignant tumor of mesenchymal origin
A
Sarcoma
16
Q
Cancer of connective tissue e.g., bones, muscles, cartilage, & blood vessels
A
Sarcoma
17
Q
Bone marrow cancer
A
Leukemia
18
Q
Cancer of the immune system. There is a presence of Reed-Sternberg (giant cells)
A
Hodgkin or Non-Hodgkin Lymphoma, Multiple Myeloma
19
Q
Agents that causes change in the gene structure. May result from misread DNA through transitions and transversions, frame-shifting or broken DNA stands
A
Mutagens
20
Q
Example of mutagen
A
Genotoxic/ DNA-reactive Carcinogens
21
Q
Carcinogen: Active parent. There is no metabolism
A
Direct-acting
22
Q
Carcinogen: Metabolite. There is a presence of metabolism
A
Indirect-acting
23
Q
Damages by alkylating electrophiles
A
Direct-acting Genotoxic Carcinogens
24
Q
The development of cancer following exposure to chemical carcinogens is a relatively _____ event because of a cell’s ability to recognize and _____ DNA.
A
rare; repair
25
The DNA region containing the adduct is removed and a new patch of DNA is synthesized, using the opposite intact strand as a template.
Cut-and-Patch by Pol 1
26
In Cut-and-Patch by pol 1 DNA repair mechanism, the new DNA segment is then ______ into the DNA molecule in place of the defective one. To be effective in restoring a cell to normal, _______________ must occur prior to ____________.
spliced; repair of DNA; cell division
27
Typically repairs chemically modified nucleobases
Base Excision or Mismatch Repair of Single-base Mispairs
28
Components of Base Excision or Mismatch Repair of Single-base Mispairs
DNA Glycosylase and Apurinic endonucleases
29
Removes altered base; pol I fills the gap
DNA Glycosylase
30
Cut DNA near apurinic sites (the cut is then extended by exonucleases, and the resulting gap is repaired by DNA polymerase and ligase)
Apurinic endonucleases
31
Component of photoreactivation repair
Photolyase
32
Binds thymine-thymine cyclobutane dimer → Individual pyrimidine bases
Photolyase
33
The double-strand break on one chromosome is repaired using the information on the homologous, intact chromosome. The same chromosome was used.
Homologous recombination
34
The predominant mechanism for double-stranded DNA repair
Nonhomologous End-joining Repair of DNA
35
Disadvantage of Nonhomologous End-joining Repair of DNA: Several base pairs are ______ at the joining point. This type of deletion may produce a possible ______________________________
lost; mutagenic coding change
36
What are the 6 DNA Repair Mechanisms?
Cut-and-Patch by pol 1, Nick Translation by pol 1, Base Excision or Mismatch Repair of Single-base Mispairs, Photoreactivation Repair, Homologous Recombination, and Nonhomologous End-joining Repair of DNA
37
Chemical mutagens
Polycyclic Aromatic Hydrocarbons (PAHs), Alkylating agents (electrophilic), Aromatic amines and amides, and Butylated Hydroxyanisole (BHA), Butylated Hydroxytoluene (BHT)
38
Classify the chemical mutagen: Benzopyrene in charcoal-broiled foods, tobacco, diesel exhaust
Polycyclic Aromatic Hydrocarbons (PAHs)
39
Classify the chemical mutagen: nitrosamines and alkyl sulfates
Alkylating agents (Electrophilic)
40
Classify the chemical mutagen: aflatoxin, and cytotoxic alkylating agents
Alkylating agents (electrophilic)
41
Classify the chemical mutagen: Dyes
Aromatic amines and amides
42
Physical mutagen found from sun exposure
Non-ionizing UV radiations (UVC, UVB, and UVA)
43
Physical mutagens found from X and Gamma rays
Ionizing radiations
44
This is contraindicated for vitiligo and psoriasis patients because this compound is a photosensitizing agent, creating higher risk for cancer
Furocoumarin (Psoralen)
45
It is a non-ionizing UV radiation that does not cross the ozone layer. It has a shorter wave
UVC
46
It is a non-ionizing UV radiation that causes tanning, burning, and skin cancer. It has longer waves than UVC. It penetrates until the epidermis layer of the skin.
UVB
47
It is a non-ionizing UV radiation that causes DNA damage, skin aging and skin cancer. It penetrates until the dermis layer of the skin because of its longer waves
UVA
48
Cancer in the glands, one of the most common
Adenocarcinoma
49
This toxin came from improper drying of nuts, and it is very hepatotoxic
Aflatoxin
50
Fragments of DNA are replaced
Nick Translation by pol 1
51
Mechanisms of actions of non-genotoxic carcinogens
sustained cytotoxicity, receptor mediated, hormonal perturbation, induction of oxidative stress, modulation/alteration of methylation status, and immunosuppression
52
Sustained toxicity leads to:
spontaneous DNA mutations, allowing it to mutate and accumulate. It has persistent regenerative growth
53
Example of non-genotoxic carcinogens that functions via sustained toxicity
chloroform
54
Receptors in receptor-mediated mechanisms of action of non-genotoxic carcinogens
Constitutive Androstane Receptor (CAR), Peroxisome proliferator-activated receptor alpha (PPARα), and Aryl hydrocarbon receptor (AhR)
55
It is a P450-related receptor. Its inducers would result in liver hyperplasia (preneoplastic focal lesion)
Constitutive Androstane Receptor (CAR)
56
example of inducer of Constitutive Androstane Receptor (CAR) and CYP2B
Phenobarbital
57
binding to this receptor leads to fatty acid oxidation, usually seen in lipids or fatty components
Peroxisome proliferator-activated receptor alpha (PPARα)
58
example of non-genotoxic carcinogens that bind to Peroxisome proliferator–activated receptor alpha (PPARα)
Fibrates
59
Effect of fibrates
lower cholesterol
60
this receptor leads to immunotoxicity
Aryl hydrocarbon receptor (AhR)
61
Can be found in carbon-less copy paper, contaminated food (fishes - remove skin or fats of the contaminated food since it accumulates in the skin and fatty areas.)
polychlorinated biphenyls
62
non-genotoxic carcinogens that function via hormonal perturbation
biogenic amines, steroid hormones, tamoxifen, and peptide hormones
63
Examples of non-genotoxic carcinogens under steroid hormones
Phytoestrogens (Bisphenol A), Diethylstilbestrol
64
morning after pill that can cause vaginal/uterine cancers and cervical cancers (may also be inherited by their daughters)
Diethylstilbestrol
65
induce decrease in T3/ T4 levels and/ or increase in TSH levels
peptide hormones
66
Chemicals that function via oxidative stress
ROS formers [superoxide anion (O2-), hydroperoxyl radical (HO2), hydrogen peroxide (H2O2 ), and the hydroxyl radical (OH)]: Ethanol, Lindane, Dieldrin, Acrylonitrile
67
This causes modulation/ Alteration of methylation status
choline deficiency
68
this methylation status is negative, promoting tumor regenesis; associated with/ mutation rates (oncogenes are hypomethylated)
hypomethylation
69
this methylation status can be reversed
hypermethylation
70
these are examples of non-genotoxic carcinogens that function via immunosuppression
Phthalates, atrazine
71
These inorganic carcinogens create carcinogenic manifestations that vary and include increased risk for skin, lung, and liver tumors
Metals (As, Be, Cd, Cr, Ni, Pb)
72
These metals increase lung/respiratory tumors
Be, Ni, Cr
73
Metal that causes kidney tumors
Cd
74
Metal that causes mouth, larynx, esophagus tumors
As
75
Other factors affecting carcinogenesis
Genes, Viral infection (Oncogenic viruses), and Environmental factors
76
genetic factors affecting carcinogenesis
genetic polymorphism and mutations
77
Gene has more than one allele
genetic polymorphism
78
This gene encodes a protein capable of transforming cells in culture or inducing cancer in animals; involved in cell signaling cascades. Once it is altered, it will cause cancer (pro-cancer)
proto-oncogenes
79
Retinoblastoma Gene (Rb1), Breast CA Gene 1 (BRCA1), Wilms Tumor Gene (WT-1), p16, and p53 are classified as:
Tumor-suppressor genes
80
T/F: Risk of breast cancer, may be passed on if not manifested to the person
True
81
This tumor suppressor gene is associated with retinoblastoma (disorder) and small-cell lung carcinoma
Rb1
82
This tumor suppressor gene is associated with Li-Fraumeni syndrome (disorder) and breast, colon, lung cancers
p53
83
This tumor suppressor gene is associated with breast carcinoma
BRCA1
84
This tumor suppressor gene is associated with Wilms tumor (disorder) and lung cancer
WT-1
85
This tumor suppressor gene is associated with melanoma
p16
86
Oncogenic viruses
Retroviruses and the 7 DNA Tumor Viruses
87
A retrovirus that leads to sarcoma, which is found in chickens
Rous Sarcoma Virus (RSV)
88
What are the 7 DNA Tumor Viruses?
Simian virus 40 (SV40), Polyoma virus, Hepatitis B virus, Human Papilloma viruses (HPV), adenoviruses, herpes viruses, and Poxviruses
89
This oncogenic virus attacks the liver, and is transmissible
Hepatitis B Virus
90
This oncogenic virus is involved in brain and bone cancer induction
Simian virus 40 (SV40)
91
This oncogenic virus is involved in genital warts
Human Papilloma viruses (HPV)
92
In vitro assessment of carcinogenicity of chemicals
Ames test, mouse lymphoma assay, chinese hamster ovary (CHO) test, syrian hamster embryo (SHE), and C3H/10T½ Cell Line Transformation Assay
93
In vitro test that uses Salmonella typhimurium strains, deficient in DNA repair and unable to synthesize histidine, are treated with several doses of the test compound.
Ames Test
94
Ames Test: In the presence of a mutagenic chemical, the defective histidine gene can be mutated back to ____________ (back mutation), resulting in a restoration of bacterial growth in medium lacking histidine
Functional state
95
Used to determine whether a chemical is capable of inducing mutation in eukaryotic cells
mouse lymphoma assay
96
mouse lymphoma assay: The ability of cells in culture to acquire resistance to _________ (result of forward mutation at the thymidine kinase locus) is quantified
trifluorothymidine
97
Commonly used to assess the potential mutagenicity of chemicals with the hypoxanthine-guanine phosphoribosyltransferase (HGPRT) gene as the endpoint
Chinese Hamster Ovary (CHO) Test
98
Diploid cell transformation assay, measures carcinogenic potential of xenobiotics by assessing transformed colonies based on morphological criterion
Syrian Hamster Embryo (SHE)
99
Originally derived from fibroblasts taken from the prostate of a C3H mouse embryo
C3H/10T½ Cell Line
100
Most frequently used endpoint (after exposure to carcinogen) in C3H/10T½ Cell Line Transformation Assay
Morphological transformation of mammalian cell fibroblasts in culture
101
What are the In vivo tests for assessing carcinogenicity of chemicals?
Transgenic rodent mutation assay systems and Chronic (Two Year) Bioassay Two-year
102
Advantages of In vivo over the In vitro test systems
Take into account whole animal processes such as ADME of chemicals and their metabolites.
103
An In vivo test primarily performed in rats and is based on the X-linked phosphatidylinositol N-aceylglucosaminyltransferase subunit A
Pig-a gene mutation assay
104
__________ is involved in the production of glycosylphosphatidylinositol (GPI) anchor proteins on the cell surface.
Pig-a gene
105
Pig-a mutation assay: the assay is optimized for measuring the Pig-a mutant phenotype in peripheral blood erythrocytes by quantification of ___________ reticulocytes and red blood vessels
CD59-negative
106
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
107
Chronic (Two Year) Bioassay Two-year procedure: 2-3 dose levels of a test chemical (up to the maximum tolerated dose) and a vehicle control are administered to 50 males and 50 females (mice and rats), beginning at _________ of age, continuing throughout their lifespan
8 weeks
108
A carcinogenic factor associated with lifestyle, a chemical whose neoplasms can be found on the esophagus, liver, oropharynx and larynx
Alcohol beverage
109
A carcinogenic factor associated with lifestyle, a chemical whose neoplasms can be found on the liver
Clue: this is from the improper drying of peanuts
aflatoxins
110
A carcinogenic factor associated with lifestyle, a chemical whose neoplasms can be found on the mouth
betel chewing
111
A carcinogenic factor associated with lifestyle, a chemical whose neoplasms can be found on the breast, colon, endometrium, and gallbladder
dietary intake (fat, protein, calories)
112
A carcinogenic factor associated with lifestyle, a chemical whose neoplasms can be found on the mouth, pharynx, larynx, lung, esophagus, and bladder
tobacco smoking
113
Occupational human carcinogens that causes neoplasms on the bronchus
Asbestos, arsenic, alkylating agents, chromium and chromates, nickel, polynuclear aromatic hydrocarbons, beryllium, cadmium, and formaldehyde
114
Occupational human carcinogens that causes neoplasms on the bone marrow
Benzene, and ethylene oxide
115
Occupational human carcinogens that causes neoplasms on the nasal sinus
chromium and chromates, nickel, wood dust, and formaldehyde
116
Occupational human carcinogens that causes neoplasms on the liver
arsenic, vinyl chloride monomer, and polychlorinated biphenyls
117
Occupational human carcinogens that causes neoplasms on the scrotum
polynuclear aromatic hydrocarbons
118
Occupational human carcinogens that causes neoplasms on the peritoneum
asbestos
119
Occupational human carcinogens that causes neoplasms on the skin
arsenic, and polynuclear aromatic hydrocarbons
120
Occupational human carcinogens that causes neoplasms on the urinary bladder
benzidine and B-naphthylamine
121
A human carcinogenic chemical associated with medical therapy and diagnosis, whose neoplasms are associated with the bladder and leukemia
alkylating agents (cyclophosphamide, melphalan)
122
A human carcinogenic chemical associated with medical therapy and diagnosis, whose neoplasms are associated with the lymphoma, reticulum cell sarcoma, skin, Kaposi sarcoma
Azathioprine
123
A human carcinogenic chemical associated with medical therapy and diagnosis, whose neoplasms are associated with leukemia
chloramphenicol
124
A human carcinogenic chemical associated with medical therapy and diagnosis, whose neoplasms are associated with the vagina (clear cell carcinoma)
Diethylstilbestrol
125
A human carcinogenic chemical associated with medical therapy and diagnosis, whose neoplasms are associated with the liver cell adenoma, endometrium, skin
estrogens
126
A human carcinogenic chemical associated with medical therapy and diagnosis, whose neoplasms are associated with the renal pelvis (carcinoma)
phenacetin
127
A human carcinogenic chemical associated with medical therapy and diagnosis, whose neoplasms are associated with the lymphoma and neuroblastoma
phenytoin
128
A human carcinogenic chemical associated with medical therapy and diagnosis, whose neoplasms are associated with the liver (angiosarcoma)
thorotrast
129
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
130
Who is the prettiest poison you've ever seen?
Andre Martin E. Marapao
