Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
42 Cards in this Set
- Front
- Back
What is a DIRECT-ACTING CARCINOGEN?
|
does not to need to be chemically altered to act (usually weak carcinogens)
|
|
What is an INDIRECT-ACTING CARCINOGEN?
|
needs metabolic conversion from PROCARCINOGEN to ULTIMATE CARCINOGEN
|
|
What are the 2 stages of chemical carcinogenesis?
|
1. initiation (carcinogenic agent irreversibly damages DNA (is mutagenic))
2. promotion (acts (reversibly) to stimulate cell proliferation and enhance carcinogenic process, but not carcinogenic in itself) |
|
How does UV radiation cause cancer? What is the extreme disease example of this process?
|
induces thymine dimers; XERODERMA PIGMENTOSUM (failure of DNA excision repair mechanisms)
|
|
What gene does v-sis mimic?
|
gene for beta chain of PDGF
|
|
What the 4 classes of regulatory genes are the principal targets of genetic damage?
|
proto-oncogenes, cancer suppressor genes, genes that regulate apoptosis, DNA repair genes
|
|
How do oncoproteins differ from the protein products of proto-oncogenes?
|
oncoproteins are devoid of important regulatory elements, their production is not dependent on growth factors or external signals
|
|
What are some examples of cancers that result from ionizing radiation?
|
-skin cancer/myeloid leukemias in radiologists
-lung cancer in uranium miners -thyroid cancer in pts w/head/neck radiation therapy -acute and chronic myeloid leukemias in atomic blast survivors -osteosarcoma in radium watch-dial workers |
|
What are the 3 oncogenic DNA viruses?
|
HPV (human papillomavirus), HBV (hep B), EBV (epstein-barr)
|
|
What is the general carcinogenic mechanism of DNA viruses?
|
integrate viral DNA into host genomes, resulting in host expression of viral mRNA coding for specific proteins
|
|
What are the major types of neoplasms implicated by HPV?
|
genital tract neoplasms, esp. premalignant lesions and cancers of cervix (sexually transmitted); laryngeal papillomas; benign squamous papillomas (warts)
|
|
What major types of neoplasms are implicated by EBV?
|
-Burkitt's lymphoma = tumor of B lymphocytes (stimulates prolif of B cells, inc opportunity for translocation and oncogene activation)
-nasopharyngeal cancer |
|
What major types of neoplasms are implicated by HBV?
|
hepatocellular carcinoma
|
|
What is the general carcinogenic mechanism of retroviruses?
|
transcription of viral genomic RNA into DNA by viral reverse transcriptase (can encode for a viral oncogene itself, or encode for a promoter sequence that is inserted near a protooncogene)
|
|
What is the only known oncogenic retrovirus? What type of neoplasm does it cause?
|
human t-cell leukemia virus type I (HTLV-1); t cell leukemia/lymphoma
|
|
What are the general downstream effect of ras?
|
activates regulators of proliferation, including kinases, which flood nucleus w/signals for cell prolif
|
|
What protein mediates the "on-off" activity of ras, by making sure ras turns off shortly after activation?
|
GAP (GTPase-activating protein) -- hydrolyzes ras-GTP to ras-GDP
|
|
What is the resulting defect when there is a mutation of the ras gene?
|
mutant ras proteins bind GAP but fail to be inactivated, thus signal is always on
|
|
What is the single most common oncogene abnormality in human tumors?
|
mutation of ras gene (25-30%)
|
|
What are some examples of oncogenes that regulate transcription of DNA in the nucleus?
|
myc, fos, myb
|
|
How does pRB regulate the cell cycle?
|
guardian of G1->S checkpoint; CDKs (activated by cyclin) phosphorylate pRB which allows entry of cells in to S phase
|
|
What is an example of oncogene activation by point mutation?
|
ras
|
|
What is insertional mutagenesis?
|
insertion of retroviral promoter or enhancer sequence into host genome that leads to inc expression of nearby oncogene
|
|
What is the translocation that occurs in Burkitt's lymphoma?
|
8:14; c-myc proto-oncogene is translocated adjacent to Ig heavy chain (region w/hectic transcriptional activity), and inc expression of c-myc
|
|
What is the translocation that occurs in chronic myeloid leukemia (CML)?
|
9:22; c-abl protooncogene is translocated adjacent to bcr locus; the c-abl-bcr hybrid (on the "Philadelphia chromosome") encodes for a protein with inc tyrosine kinase activity
|
|
What is the translocation in acute promyelocytic leukemia?
|
15:17; results in fusion of retinoic acid receptor (RAR-alpha) and transcriptional unit PM
*can induce remission w/all-trans retinoic acid (vit A analogue)* |
|
What do "double-minutes" and "homogenous staining regions" on chromosomes indicate?
|
extensive gene amplification
|
|
What are 2 types of neoplasms which involve amplification, and what genes are amplified?
|
neuroblastoma (N-myc) -> correlates strongly w/disease progression
breast cancers (c-erbB2) -> associated w/poor prognosis |
|
What is the two-hit hypothesis of Knudson?
|
2 mutations are required to express neoplastic phenotype (both alleles must be inactivated)
|
|
What is the prototypic cancer suppressor gene for which the two-hit hypothesis applies?
|
Rb gene--inactivation causes retinoblastoma (childhood tumor)
|
|
How is the cell cycle affected if the Rb gene is inactivated?
|
normally, cell cycle can only move to S phase if pRb is phosphorylated, setting free transcription factors. if pRb is absent, "molecular breaks" of cell cycle are gone, cells proceed easily into S phase
|
|
What is the most common target for genetic alteration in human tumors?
|
p53
|
|
What is the normal function of p53?
|
causes cell cycle arrest in G1 when there is DNA damage, so it can be repaired. if damage is not repaired, p53 induces apoptosis
|
|
What syndrome results from familial loss of p53, and what is this syndrome characterized by?
|
Li-Fraumeni syndrome; wide variety of tumors (breast, soft tissue carcinomas, brain tumors, leukemias, etc)
|
|
What are some major cancer suppressor genes?
|
Rb, p53, WT-1, BCRA-1, APC, NF-1
|
|
What syndrome results from deletion or inactivation of WT-1?
|
Wilms tumor (most common renal neoplasm in children)
(WT-1 = Wilms Tumor-1) |
|
What types of neoplasms result from inactivation of APC?
|
familial polyposis coli and adenocarcinoma of colon
(APC = adenomatous polyposis coli) |
|
What types of neoplasms result from inactivation from BRCA-1?
|
familial propensity to breast and ovarian cancers
(BRCA-1 = BReast CAncer-1) |
|
What are some common genes associated with apoptosis?
|
bcl-2, bax, p53 (by increasing transcription of bax)
|
|
What is the molecular defect in hereditary nonpolyposis colon carcinoma (HNPCC or Lynch syndrome)?
|
mutation in DNA mismatch repair genes
|
|
What is the genetic defect in von Recklinghausen neurofibromatosis type 1?
|
mutations in NF-1 tumor suppressor gene (which fns as a GAP protein that inactivates ras)
|
|
What is the genetic defect in multiple endocrine neoplasia type IIa?
|
mutations in ret protooncogene transmitted in germline
|