Chemical Carcinogenesis Flashcards
Abnormal cell differentiation and growth
Cancer/Neoplasm
In all types of cancer, some of the body’s cells begin to ______ without stopping and ______ into surrounding tissues
Divide; spread
1 cm tumor (~1g) = _______ cancer cells
1 billion (10⁹)
1 kg = ______ cancer cells
10¹² (1 trillion)
Characteristics of Cancer:
- __________ in growth signals
- __________ to antigrowth signals
- __________ of apoptosis
- Limitless __________ potential
- Tissue _________ and _________
- Sustained ___________
- Self-sufficiency
- Insensitivity
- Evasion
- Replicative
- Invasion; metastasis
- Angiogenesis
One of the characteristics of cancer is the spread outside of its original location. What is that term?
Metastasis
In cancer, there is formation of new blood vessels. What is that term?
Angiogenesis
Reversible stage of carcinogenesis by stopping the tumor promoter of the one responsible of spreading the damaged cells but only until initiation
Promotion
Triggered by tumor promoter
Initiated cell
The first stage of carcinogenesis
Initiation
Irreversible stages of carcinogenesis
Initiation and progression
Abnormal tissue growth in mucosal surface of colon (most common), ear canal, cervix.
Benign Tumors / Polyp
Malignant tumor of epithelial origin
Carcinoma
Most common. Cancer of the skin or organ lining e.g., liver or kidneys
Carcinoma
Malignant tumor of mesenchymal origin
Sarcoma
Cancer of connective tissue e.g., bones, muscles, cartilage, & blood vessels
Sarcoma
Bone marrow cancer
Leukemia
Cancer of the immune system. There is a presence of Reed-Sternberg (giant cells)
Hodgkin or Non-Hodgkin Lymphoma, Multiple Myeloma
Agents that causes change in the gene structure. May result from misread DNA through transitions and transversions, frame-shifting or broken DNA stands
Mutagens
Example of mutagen
Genotoxic/ DNA-reactive Carcinogens
Carcinogen: Active parent. There is no metabolism
Direct-acting
Carcinogen: Metabolite. There is a presence of metabolism
Indirect-acting
Damages by alkylating electrophiles
Direct-acting Genotoxic Carcinogens
The development of cancer following exposure to chemical carcinogens is a relatively _____ event because of a cell’s ability to recognize and _____ DNA.
rare; repair
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
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
Typically repairs chemically modified nucleobases
Base Excision or Mismatch Repair of Single-base Mispairs
Components of Base Excision or Mismatch Repair of Single-base Mispairs
DNA Glycosylase and Apurinic endonucleases
Removes altered base; pol I fills the gap
DNA Glycosylase
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
Component of photoreactivation repair
Photolyase
Binds thymine-thymine cyclobutane dimer → Individual pyrimidine bases
Photolyase
The double-strand break on one chromosome is repaired using the information on the homologous, intact chromosome. The same chromosome was used.
Homologous recombination
The predominant mechanism for double-stranded DNA repair
Nonhomologous End-joining Repair of DNA
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
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
Chemical mutagens
Polycyclic Aromatic Hydrocarbons (PAHs), Alkylating agents (electrophilic), Aromatic amines and amides, and Butylated Hydroxyanisole (BHA), Butylated Hydroxytoluene (BHT)
Classify the chemical mutagen: Benzopyrene in charcoal-broiled foods, tobacco, diesel exhaust
Polycyclic Aromatic Hydrocarbons (PAHs)
Classify the chemical mutagen: nitrosamines and alkyl sulfates
Alkylating agents (Electrophilic)
Classify the chemical mutagen: aflatoxin, and cytotoxic alkylating agents
Alkylating agents (electrophilic)
Classify the chemical mutagen: Dyes
Aromatic amines and amides
Physical mutagen found from sun exposure
Non-ionizing UV radiations (UVC, UVB, and UVA)
Physical mutagens found from X and Gamma rays
Ionizing radiations
This is contraindicated for vitiligo and psoriasis patients because this compound is a photosensitizing agent, creating higher risk for cancer
Furocoumarin (Psoralen)
It is a non-ionizing UV radiation that does not cross the ozone layer. It has a shorter wave
UVC
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
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
Cancer in the glands, one of the most common
Adenocarcinoma
This toxin came from improper drying of nuts, and it is very hepatotoxic
Aflatoxin
Fragments of DNA are replaced
Nick Translation by pol 1
Mechanisms of actions of non-genotoxic carcinogens
sustained cytotoxicity, receptor mediated, hormonal perturbation, induction of oxidative stress, modulation/alteration of methylation status, and immunosuppression
Sustained toxicity leads to:
spontaneous DNA mutations, allowing it to mutate and accumulate. It has persistent regenerative growth