Chemical Carcinogenesis Flashcards

1
Q

Abnormal cell differentiation and growth

A

Cancer/Neoplasm

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2
Q

In all types of cancer, some of the body’s cells begin to ______ without stopping and ______ into surrounding tissues

A

Divide; spread

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3
Q

1 cm tumor (~1g) = _______ cancer cells

A

1 billion (10⁹)

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4
Q

1 kg = ______ cancer cells

A

10¹² (1 trillion)

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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
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6
Q

One of the characteristics of cancer is the spread outside of its original location. What is that term?

A

Metastasis

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7
Q

In cancer, there is formation of new blood vessels. What is that term?

A

Angiogenesis

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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

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9
Q

Triggered by tumor promoter

A

Initiated cell

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10
Q

The first stage of carcinogenesis

A

Initiation

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11
Q

Irreversible stages of carcinogenesis

A

Initiation and progression

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12
Q

Abnormal tissue growth in mucosal surface of colon (most common), ear canal, cervix.

A

Benign Tumors / Polyp

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13
Q

Malignant tumor of epithelial origin

A

Carcinoma

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14
Q

Most common. Cancer of the skin or organ lining e.g., liver or kidneys

A

Carcinoma

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15
Q

Malignant tumor of mesenchymal origin

A

Sarcoma

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16
Q

Cancer of connective tissue e.g., bones, muscles, cartilage, & blood vessels

A

Sarcoma

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17
Q

Bone marrow cancer

A

Leukemia

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18
Q

Cancer of the immune system. There is a presence of Reed-Sternberg (giant cells)

A

Hodgkin or Non-Hodgkin Lymphoma, Multiple Myeloma

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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

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20
Q

Example of mutagen

A

Genotoxic/ DNA-reactive Carcinogens

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21
Q

Carcinogen: Active parent. There is no metabolism

A

Direct-acting

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22
Q

Carcinogen: Metabolite. There is a presence of metabolism

A

Indirect-acting

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23
Q

Damages by alkylating electrophiles

A

Direct-acting Genotoxic Carcinogens

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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

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25
Q

The DNA region containing the adduct is removed and a new patch of DNA is synthesized, using the opposite intact strand as a template.

A

Cut-and-Patch by Pol 1

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26
Q

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 ____________.

A

spliced; repair of DNA; cell division

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27
Q

Typically repairs chemically modified nucleobases

A

Base Excision or Mismatch Repair of Single-base Mispairs

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28
Q

Components of Base Excision or Mismatch Repair of Single-base Mispairs

A

DNA Glycosylase and Apurinic endonucleases

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29
Q

Removes altered base; pol I fills the gap

A

DNA Glycosylase

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30
Q

Cut DNA near apurinic sites (the cut is then extended by exonucleases, and the resulting gap is repaired by DNA polymerase and ligase)

A

Apurinic endonucleases

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31
Q

Component of photoreactivation repair

A

Photolyase

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32
Q

Binds thymine-thymine cyclobutane dimer → Individual pyrimidine bases

A

Photolyase

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33
Q

The double-strand break on one chromosome is repaired using the information on the homologous, intact chromosome. The same chromosome was used.

A

Homologous recombination

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34
Q

The predominant mechanism for double-stranded DNA repair

A

Nonhomologous End-joining Repair of DNA

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35
Q

Disadvantage of Nonhomologous End-joining Repair of DNA: Several base pairs are ______ at the joining point. This type of deletion may produce a possible ______________________________

A

lost; mutagenic coding change

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36
Q

What are the 6 DNA Repair Mechanisms?

A

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

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37
Q

Chemical mutagens

A

Polycyclic Aromatic Hydrocarbons (PAHs), Alkylating agents (electrophilic), Aromatic amines and amides, and Butylated Hydroxyanisole (BHA), Butylated Hydroxytoluene (BHT)

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38
Q

Classify the chemical mutagen: Benzopyrene in charcoal-broiled foods, tobacco, diesel exhaust

A

Polycyclic Aromatic Hydrocarbons (PAHs)

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39
Q

Classify the chemical mutagen: nitrosamines and alkyl sulfates

A

Alkylating agents (Electrophilic)

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40
Q

Classify the chemical mutagen: aflatoxin, and cytotoxic alkylating agents

A

Alkylating agents (electrophilic)

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41
Q

Classify the chemical mutagen: Dyes

A

Aromatic amines and amides

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42
Q

Physical mutagen found from sun exposure

A

Non-ionizing UV radiations (UVC, UVB, and UVA)

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43
Q

Physical mutagens found from X and Gamma rays

A

Ionizing radiations

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44
Q

This is contraindicated for vitiligo and psoriasis patients because this compound is a photosensitizing agent, creating higher risk for cancer

A

Furocoumarin (Psoralen)

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45
Q

It is a non-ionizing UV radiation that does not cross the ozone layer. It has a shorter wave

A

UVC

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46
Q

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.

A

UVB

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47
Q

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

A

UVA

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48
Q

Cancer in the glands, one of the most common

A

Adenocarcinoma

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49
Q

This toxin came from improper drying of nuts, and it is very hepatotoxic

A

Aflatoxin

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50
Q

Fragments of DNA are replaced

A

Nick Translation by pol 1

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51
Q

Mechanisms of actions of non-genotoxic carcinogens

A

sustained cytotoxicity, receptor mediated, hormonal perturbation, induction of oxidative stress, modulation/alteration of methylation status, and immunosuppression

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52
Q

Sustained toxicity leads to:

A

spontaneous DNA mutations, allowing it to mutate and accumulate. It has persistent regenerative growth

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53
Q

Example of non-genotoxic carcinogens that functions via sustained toxicity

A

chloroform

54
Q

Receptors in receptor-mediated mechanisms of action of non-genotoxic carcinogens

A

Constitutive Androstane Receptor (CAR), Peroxisome proliferator-activated receptor alpha (PPARα), and Aryl hydrocarbon receptor (AhR)

55
Q

It is a P450-related receptor. Its inducers would result in liver hyperplasia (preneoplastic focal lesion)

A

Constitutive Androstane Receptor (CAR)

56
Q

example of inducer of Constitutive Androstane Receptor (CAR) and CYP2B

A

Phenobarbital

57
Q

binding to this receptor leads to fatty acid oxidation, usually seen in lipids or fatty components

A

Peroxisome proliferator-activated receptor alpha (PPARα)

58
Q

example of non-genotoxic carcinogens that bind to Peroxisome proliferator–activated receptor alpha (PPARα)

A

Fibrates

59
Q

Effect of fibrates

A

lower cholesterol

60
Q

this receptor leads to immunotoxicity

A

Aryl hydrocarbon receptor (AhR)

61
Q

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.)

A

polychlorinated biphenyls

62
Q

non-genotoxic carcinogens that function via hormonal perturbation

A

biogenic amines, steroid hormones, tamoxifen, and peptide hormones

63
Q

Examples of non-genotoxic carcinogens under steroid hormones

A

Phytoestrogens (Bisphenol A), Diethylstilbestrol

64
Q

morning after pill that can cause vaginal/uterine cancers and cervical cancers (may also be inherited by their daughters)

A

Diethylstilbestrol

65
Q

induce decrease in T3/ T4 levels and/ or increase in TSH levels

A

peptide hormones

66
Q

Chemicals that function via oxidative stress

A

ROS formers [superoxide anion (O2-), hydroperoxyl radical (HO2), hydrogen peroxide (H2O2 ), and the hydroxyl radical (OH)]: Ethanol, Lindane, Dieldrin, Acrylonitrile

67
Q

This causes modulation/ Alteration of methylation status

A

choline deficiency

68
Q

this methylation status is negative, promoting tumor regenesis; associated with/ mutation rates (oncogenes are hypomethylated)

A

hypomethylation

69
Q

this methylation status can be reversed

A

hypermethylation

70
Q

these are examples of non-genotoxic carcinogens that function via immunosuppression

A

Phthalates, atrazine

71
Q

These inorganic carcinogens create carcinogenic manifestations that vary and include increased risk for skin, lung, and liver tumors

A

Metals (As, Be, Cd, Cr, Ni, Pb)

72
Q

These metals increase lung/respiratory tumors

A

Be, Ni, Cr

73
Q

Metal that causes kidney tumors

A

Cd

74
Q

Metal that causes mouth, larynx, esophagus tumors

A

As

75
Q

Other factors affecting carcinogenesis

A

Genes, Viral infection (Oncogenic viruses), and Environmental factors

76
Q

genetic factors affecting carcinogenesis

A

genetic polymorphism and mutations

77
Q

Gene has more than one allele

A

genetic polymorphism

78
Q

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)

A

proto-oncogenes

79
Q

Retinoblastoma Gene (Rb1), Breast CA Gene 1 (BRCA1), Wilms Tumor Gene (WT-1), p16, and p53 are classified as:

A

Tumor-suppressor genes

80
Q

T/F: Risk of breast cancer, may be passed on if not manifested to the person

A

True

81
Q

This tumor suppressor gene is associated with retinoblastoma (disorder) and small-cell lung carcinoma

A

Rb1

82
Q

This tumor suppressor gene is associated with Li-Fraumeni syndrome (disorder) and breast, colon, lung cancers

A

p53

83
Q

This tumor suppressor gene is associated with breast carcinoma

A

BRCA1

84
Q

This tumor suppressor gene is associated with Wilms tumor (disorder) and lung cancer

A

WT-1

85
Q

This tumor suppressor gene is associated with melanoma

A

p16

86
Q

Oncogenic viruses

A

Retroviruses and the 7 DNA Tumor Viruses

87
Q

A retrovirus that leads to sarcoma, which is found in chickens

A

Rous Sarcoma Virus (RSV)

88
Q

What are the 7 DNA Tumor Viruses?

A

Simian virus 40 (SV40), Polyoma virus, Hepatitis B virus, Human Papilloma viruses (HPV), adenoviruses, herpes viruses, and Poxviruses

89
Q

This oncogenic virus attacks the liver, and is transmissible

A

Hepatitis B Virus

90
Q

This oncogenic virus is involved in brain and bone cancer induction

A

Simian virus 40 (SV40)

91
Q

This oncogenic virus is involved in genital warts

A

Human Papilloma viruses (HPV)

92
Q

In vitro assessment of carcinogenicity of chemicals

A

Ames test, mouse lymphoma assay, chinese hamster ovary (CHO) test, syrian hamster embryo (SHE), and C3H/10T½ Cell Line Transformation Assay

93
Q

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.

A

Ames Test

94
Q

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

A

Functional state

95
Q

Used to determine whether a chemical is capable of inducing mutation in eukaryotic cells

A

mouse lymphoma assay

96
Q

mouse lymphoma assay: The ability of cells in culture to acquire resistance to _________ (result of forward mutation at the thymidine kinase locus) is quantified

A

trifluorothymidine

97
Q

Commonly used to assess the potential mutagenicity of chemicals with the hypoxanthine-guanine phosphoribosyltransferase (HGPRT) gene as the endpoint

A

Chinese Hamster Ovary (CHO) Test

98
Q

Diploid cell transformation assay, measures carcinogenic potential of xenobiotics by assessing transformed colonies based on morphological criterion

A

Syrian Hamster Embryo (SHE)

99
Q

Originally derived from fibroblasts taken from the prostate of a C3H mouse embryo

A

C3H/10T½ Cell Line

100
Q

Most frequently used endpoint (after exposure to carcinogen) in C3H/10T½ Cell Line Transformation Assay

A

Morphological transformation of mammalian cell fibroblasts in culture

101
Q

What are the In vivo tests for assessing carcinogenicity of chemicals?

A

Transgenic rodent mutation assay systems and Chronic (Two Year) Bioassay Two-year

102
Q

Advantages of In vivo over the In vitro test systems

A

Take into account whole animal processes such as ADME of chemicals and their metabolites.

103
Q

An In vivo test primarily performed in rats and is based on the X-linked phosphatidylinositol N-aceylglucosaminyltransferase subunit A

A

Pig-a gene mutation assay

104
Q

__________ is involved in the production of glycosylphosphatidylinositol (GPI) anchor proteins on the cell surface.

A

Pig-a gene

105
Q

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

A

CD59-negative

106
Q

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

A

Chronic (Two Year) Bioassay

107
Q

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

A

8 weeks

108
Q

A carcinogenic factor associated with lifestyle, a chemical whose neoplasms can be found on the esophagus, liver, oropharynx and larynx

A

Alcohol beverage

109
Q

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

A

aflatoxins

110
Q

A carcinogenic factor associated with lifestyle, a chemical whose neoplasms can be found on the mouth

A

betel chewing

111
Q

A carcinogenic factor associated with lifestyle, a chemical whose neoplasms can be found on the breast, colon, endometrium, and gallbladder

A

dietary intake (fat, protein, calories)

112
Q

A carcinogenic factor associated with lifestyle, a chemical whose neoplasms can be found on the mouth, pharynx, larynx, lung, esophagus, and bladder

A

tobacco smoking

113
Q

Occupational human carcinogens that causes neoplasms on the bronchus

A

Asbestos, arsenic, alkylating agents, chromium and chromates, nickel, polynuclear aromatic hydrocarbons, beryllium, cadmium, and formaldehyde

114
Q

Occupational human carcinogens that causes neoplasms on the bone marrow

A

Benzene, and ethylene oxide

115
Q

Occupational human carcinogens that causes neoplasms on the nasal sinus

A

chromium and chromates, nickel, wood dust, and formaldehyde

116
Q

Occupational human carcinogens that causes neoplasms on the liver

A

arsenic, vinyl chloride monomer, and polychlorinated biphenyls

117
Q

Occupational human carcinogens that causes neoplasms on the scrotum

A

polynuclear aromatic hydrocarbons

118
Q

Occupational human carcinogens that causes neoplasms on the peritoneum

A

asbestos

119
Q

Occupational human carcinogens that causes neoplasms on the skin

A

arsenic, and polynuclear aromatic hydrocarbons

120
Q

Occupational human carcinogens that causes neoplasms on the urinary bladder

A

benzidine and B-naphthylamine

121
Q

A human carcinogenic chemical associated with medical therapy and diagnosis, whose neoplasms are associated with the bladder and leukemia

A

alkylating agents (cyclophosphamide, melphalan)

122
Q

A human carcinogenic chemical associated with medical therapy and diagnosis, whose neoplasms are associated with the lymphoma, reticulum cell sarcoma, skin, Kaposi sarcoma

A

Azathioprine

123
Q

A human carcinogenic chemical associated with medical therapy and diagnosis, whose neoplasms are associated with leukemia

A

chloramphenicol

124
Q

A human carcinogenic chemical associated with medical therapy and diagnosis, whose neoplasms are associated with the vagina (clear cell carcinoma)

A

Diethylstilbestrol

125
Q

A human carcinogenic chemical associated with medical therapy and diagnosis, whose neoplasms are associated with the liver cell adenoma, endometrium, skin

A

estrogens

126
Q

A human carcinogenic chemical associated with medical therapy and diagnosis, whose neoplasms are associated with the renal pelvis (carcinoma)

A

phenacetin

127
Q

A human carcinogenic chemical associated with medical therapy and diagnosis, whose neoplasms are associated with the lymphoma and neuroblastoma

A

phenytoin

128
Q

A human carcinogenic chemical associated with medical therapy and diagnosis, whose neoplasms are associated with the liver (angiosarcoma)

A

thorotrast

129
Q

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.

A

Cancer

130
Q

Who is the prettiest poison you’ve ever seen?

A

Andre Martin E. Marapao