Pathology of Neoplasia (22)

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List 3 broad carcinogenic agents.

chemical agents

physical agents

oncogenic virus

bacterial infection

What type of carcinogens require metabolic conversion by cytochrome P450 in the liver?

indirect acting

Review some chemical carcinogens.

Review some major chemical carcinogens.

What are the 2 players in chemical carcinogenesis?

initiator: causes mutation in cell

promotor: causes clonal expansion of initiated cells through enzyme activation or by mutation

Name 2 types of radiation that can be carcinogenic.

UV rays

ionizing radiation

What 2 factors determine the degree of damage due to UV radiation?

intensit of exposure and quantity

What type of radiation causes DNA damage due to formation of pyrimidine dimers?

UV rays

What is the normal mechanism of repair of pyrimidine dimers?

nucleotide excision repair (NER)

List 3 cancers caused by UV radiation.

squamous cell carcinoma

basal cell carcinoma

melanoma

List 3 ways in which ionizing radiation is carcinogenic.

DNA damage

alters proteins

inactivates enzymes

injures membranes

ionization of macromolecules and generation of free radicals

Most oncogenic viruses have what type of nucleic acid?

DNA

Name 3 major DNA oncogenic viruses.

HPV

EBV

HBV

Virus that causes cervical cancer.

HPV

Virus that causes nasopharyngeal carcinoma.

EBV

Virus that causes hepatocellular carcinoma.

HBV

What type of genes are affected by oncogenic viruses?

tumor suppressor genes

Review EBV and Burkitt's lymphoma.

Name the most important RNA oncogenic virus.

HTLV-1

How does HTLV-1 cause tumor formation?

Tax causes instability and mutation in host cell genes leading to T-cell proliferation

What bacteria is associated with B-cell lymphoma in MALT?

H. pylori

List 4 classes of genes affected by carcinogens.

oncogenes

tumor suppressor genes

apoptosis regulating genes

mutator (caretaker) genes

Normal genes that play key roles in controlling cell proliferation and differentiation.

proto-oncogenes

Deregulated or altered proto-oncogenes that lead to development of cancer.

oncogenes

List 3 changes in gene structure that can cause activation of oncogenes.

point mutation

translocation

amplification

What is the most common point mutation in human cancers?

RAS mutation

Name the 2 chromosomes involved in translocation for chronic myelogenous leukemia.

9, 22

What enzyme activity is increased in chronic myelogenous leukemia?

tyrosine kinase

Amplification of which gene is involved in neuroblastoma?

N-MYC

Amplification of which gene is involved in breast cancer?

HER2

What type of proteins are encoded by oncogenes?

oncoproteins

List 5 classes of oncoproteins.

growth factors

growth factor receptors

signal transduction proteins

nuclear (transcription) regulatory factors

cyclin and cyclin-dependent kinases (cell cycle)

Review cell membrane diagram.

What is the most commonly mutated tumor suppressor gene?

p53

Name a tumor suppressor gene that acts on the cell cycle (G1-S).

retinoblastoma

How many alleles must be mutated to disrupt the function of tumor suppressor genes?

both (homozygous mutation)

Tumor suppressor gene associated with hereditary neurofibromatosis.

NF1

Tumor suppressor genes associated with breast carcinoma.

BRCA 1 & 2

Tumor suppressor gene associated with adenomatous polyposis cell carcinoma.

APC

Tumor suppressor gene associated with colon cancer.

DCC

Tumor suppressor gene associated with Wilm's tumor.

WT-1

What happens to telomeres with age?

telomeres shortened with age

Gene associated with colon and pancreatic cancers.

KRAS

Gene associated with B-cell lymphomas.

BCL2

Review multistep carcinogenesis.

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