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.Pathology 1 > Carcinogenesis > Flashcards

Carcinogenesis Flashcards

1
Q

contrast direct vs. indirect acting carcinogens

A
  • direct acting: weak carcinogens - dose and time dependent
  • indirect acting: requires metabolic conversion – (cytochrome P450 in liver)
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2
Q

what is the effect of direct acting alkylating agents?

A

cyclophosphamide –> leukemia

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3
Q

what is the effect of polycyclic aromatic hydrocarbons?

A

tobacco –> lung cancer

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4
Q

what is the effect of aromatic amines and azodyes?

A

hepatocellular cancer, bladder cancer

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5
Q

what is the effect of nitrosamines and amides?

A

gastric cancer

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6
Q

what is the effect of asbestos?

A

mesothelioma, lung cancer

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7
Q

describe the mechanism of chemical carcinogenesis

A
  • initiator causes mutation in the cell
  • promoter causes clonal expansion
  • may act at the DNA, RNA or protein level
  • both agents are needed for carcinogenesis
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8
Q

describe UV radiation

A
  • the degrees of risk depend on:
    • the intensity of exposure and quantity
  • mechanisms
    • DNA damage
    • formation of pyrimidine dimers
    • nucleotide excision repair (NER) mechanism may be overwhelmed
  • e.g.: squamous cell CA, basal cell CA, melanoma
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9
Q

describe ionizing radiation

A
  • electromagnetic radiation (x-ray) is carcinogenic
  • atomic bomb = increased leukemia
  • therapeutic irradiation = thyroid cancer
  • radiant energy:
    • DNA damage
    • alters proteins
    • inactivates enzymes
    • injures membranes
    • ionization of macromolecules and generation of free radicals
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10
Q

list the DNA oncogenic viruses

A
  • HPV
    • papilloma (skin, larynx)
    • cervical cancer
  • EBV
    • nasopharyngeal carcinoma
    • Burkitt’s lymphoma
  • HBV
    • hepatocellular carcinoma
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11
Q

describe carcinogenesis by HPV

A
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12
Q

describe how EB virus leads to development of Burkitt’s lymphoma

A
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13
Q

describe the RNA oncogenic viruses

A
  • RNA oncogenic viruses are retroviruses (contain reverse transcriptase)
  • RNA oncogenic viruses:
    • acute transforming
    • slow transforming
    • human T-cell leukemia virus (HTLV-1)
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14
Q

describe HTLV-1

A
  • RNA virus implicated in human cancer
  • associated with human T-cell leukemia/lymphoma
  • viral Tax protein stimulates proliferation, enhances cell survival and interferes with cell cycle controls
  • proliferation initially is polyclonal
  • secondary mutations lead to the outgrowth of monoclonal leukemia
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15
Q

list the important oncogenic viruses

A
  • EBV = Burkitts lymphoma/nasopharyngeal cancer
  • HHV-8 = Kaposi’s sarcoma
  • HBV/HCV = hepatocellular cancer
  • HTLV = human T cell leukemia/lymphoma
  • HPV = squamous cell carcinoma of vulva, vagina, anus, cervix
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16
Q

describe bacterial infections involved in carcinogenesis

A
  • H. pylori infection is associated with B cell lymphoma in the mucosa associated lymphatic tissue (MALToma)
17
Q

describe driver vs. passenger mutations

A
18
Q

describe genetic changes in tumors

A
  • the genetic changes in tumors may be:
    • small (point mutations) KRAS - colon cancer
    • large (chromosomal/karyotypic) changes
  • balanced translocation
    • CML = t(9,22)
    • Burkitt’s lymphoma = t(8,14)
  • deletion: retionblastoma –> del 13q14
  • gene amplification: neuroblastoma –> NMYC
19
Q

describe proto-oncogenes vs. oncogenes

A
  • proto-oncogenes: normal genes that play key roles in controlling cell proliferation and differentiation
  • oncogenes: deregulated or altered proto-oncogenes that lead to development of cancer
20
Q

describe point mutations in genes leading to cancer

A
  • RAS (oncogene) mutation is the most common mutation in human cancers
  • also occurs in tumor suppressor gene TP53
21
Q

describe translocations leading to cancers

A
22
Q

describe gene amplification leading to cancer

A
23
Q

describe growth factor oncoproteins

A
  • growth factors:
    • mutation of growth factor genes –> oncogenic
    • PDGF –> astrocytoma​
24
Q

describe growth factor receptor oncoproteins

A
  • growth factor receptors
    • oncogenes may encode mutated form of receptors
    • ERBB2 (HER2/neu) –> epidermal growth factor receptor - amplification –> breast cancer/stomach cancer
25
Q

describe signal transduction protein oncoproteins

A
  • oncoprotein mimics function of signal transduction proteins
    • ABL (tyrosine kinase) - CML t(9,22) with BCR, some ALL
    • RAS (GTP binding protein) - carcinomas, point mutation
26
Q

describe nuclear regulatory factor oncoproteins

A
  • oncoproteins regulate nuclear transcription
    • CMYC - Burkitt’s lymphoma, t(8,14) with IgH
    • NMYC - neuroblastoma (amplification)
27
Q

describe cyclin and cyclin-dependent kinases (oncoproteins)

A
  • mutation dysregulate cell cycle
    • CCND (cyclin D1): mantle cell lymphoma (t11,14) with IgH
28
Q

describe the tumor suppressor genes

A
  • inhibitors of cell proliferation: loss (mutation) causes insensitivity to growth inhibitory signals; mutation of both alleles (homozygous mutation) are necessary
  • RB gene (acts on cell cycle G1 -> S)
    • hypophosphorylated RB binds to E2F (transcription factor); RB mutation frees E2F –> proliferation
  • P53: senses DNA damage and helps repair by slowing cell cycle
    • P53 upregulates BAX which disrupts BCL2
      • lung, colon, breast, ovary cancer
29
Q

describe apoptosis regulating genes

A
30
Q

describe mutator (caretaker) genes

A
31
Q

cancer cells express the enzyme ____ which preserves ___; doesn’t shorten with each replication

A

cancer cells express the enzyme telomerase which preserves telomeres; doesn’t shorten with each replication

.Pathology 1 (15 decks)

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