Neoplasia 7: Carcinogenesis Flashcards
Difference between direct-acting and indirect-acting carcinogens? Which is the majority of chemical carcinogens? Radiation? Microbes?
Direct-acting DO NOT require metabolic conversation. Radiation and microbes are direct-acting.
Indirect-acting require metabolic conversion to an ultimate carcinogen; majority
Differences in susceptibiltiy to smoking-related lung cancer can be due to genetic polymorphisms in the ____ pathway. What does this pathway do, and why does it relate to lung cancer?
cytochrome P-450 pathway (CYP1A1 metabolizes and is induced by polycyclic aromatic hydrocarbons, or PAHs, found in cigarettes). When it does so, it makes precarcinogens into carcinogens. For those with the cancer-causing polymorphism, they have an inducible enzyme, so that in presence of carcinogen it is more likely to cause CYP1A1 to be active.
Aflatoxin B1 is a naturally occuring chemical carcinogen produced by some kinds of ____ fungus, found in improperly stored nuts/ grains. It results in ____ carcinoma, especially in regions of high consumption which include ___ and ____.
Aflatoxin B1 is a naturally occuring chemical carcinogen produced by some kinds of Aspergillus fungus, found in improperly stored nuts/ grains. It results in hepatocellular carcinoma, especially in regions of high consumption which include Africa and Southeast Asia.
Aflatoxin-related hepatocellular carcinoma has a characteristic mutation at codon 249 of ____ gene. How does this operate?
p53: Aflatoxin is more likely to bind that DNA sequence, causing characteristic changes
What is mesothelioma? What is the most important risk factor for pleural mesothelioma worldwide?
Malignancy of pleura (lining the lung): gradual onset of chest pain, dyspnea, cough, hoarseness, night sweats; poor survival after diagnosis. or of peritoneum, lining visceral abdominal organs Asbestos
What are three theories on how asbestos-induced cancer occurs?
- oxidative stress: phagocytic cells engulf asbestos, and produce DNA-damaging free radicals due to their inability to digest the fiber 2. chromosome tangling theory: asbestos fibers physically tangle with and damage chromosomes during cell division 3. adsorption theory: asbestos fibers in vivo concentrate chemicals including the components of cigarette smoke
What are the two forms of radiation?
Ionizing: EM or particle radiation (nuclear reactor, radiotherapy). has enough energy to displace electrons, create ions
Ultraviolent: non-ionizing, sunlight
What type of cancer is this, and what carcinogen is it associated with? What other two cancers are associated with this carcinogen?
Basal cell carcinoma of skin: is associated with UV light.
Basal cell carcinoma of skin; squamous cell carcinoma of skin; melanoma
What disease is associated with skin cancer by age 10, as well as neurological disorders? What is the mutation?
Xeroderma pigmentosum. Mutation causes defective nucleotide excision repair, which normally repairs DNA pyrimidine dimerization.
What is the main cancer associated with Chernobyl and other ionizing radiation carcinogen exposure? Why do many of these cancers occur?
Papillary cancer of the thyroid. Chernobyl released Iodine-131; thyroid takes up iodine.
Often due to chromosomal rearrangements, especially RET-PTC
HTLV-1 is a ___ virus which causes ________. It has a tropism for ____ cells, and transmission occurs via those infected cells through sexual intercourse, blood exchange, breastfeeding. Carcinogenesis is attributable to a gene essential for transcription of viral RNA, called ___
Adult T-cell Leukemia/Lymphoma
CD4+ T cells
tax gene
Biopsy a neck mass, and we see group of cells with high N:C ratio, occasional orange cytoplasm (keratin). How can you distinguish whether this is primary or secondary?
Carcinoma, maybe squamous cell because it’s keratin
If there are overlying skin changes, then primary; otherwise secondary
if it’s located along the chain of cervical lymph nodes, likely lymph node metastasis
HPV is associated not just with cervical cancers, but the majority in males is in __ cancers.
oropharyngeal
HPV E6 binds ___, promoting its degradation. It also activates ___.
p53, promoting p53 degradation, activation of TERT
E7 binds ____, displaces E2F transcription factor, allowing promotion of transcription of cell-cycle genes. It also inhibits ____ and activates __.
E7 binds Retinoblastoma, promoting transcription of cell-cycle genes. It inhibits CDK inhibitor p21, and activates cyclins.
