Cancer

What test is used to identify the carcinogenicty of compounds and how does it work?

Ames test - Salmonella is grown in abscence of histadine - needs high level of histadine as highly active histadine degrading enzymes - mutations in this enzyme allow salmonella to grow

Name the six traits acquired by cancerous cells:

Ability to grow and divide without outside inputs, Being insensitive to anti-growth signals, evade apoptosis, limitless reproductive capacity, sustain angiogenesis and ability to invade tissues.

Name and describe two common oncogenes:

Ras and Myc
Ras - the most common oncogene mutation, found in 30% of human tumours. Its normal role is to transmit signals from growth receptors. When inactivated ras is bound to GDP, when active it exchanges GDP for GTP and can then activate downstream proteins. The activated state is temporary as ras has intrinsic GTPase activity which returns the protein to an inactive state. Mutant ras remains in an active state causing constant activation of downstream proteins, the cell acts as if it is receiving input instructing it to proliferate.

Myc - Mutation in nuclear transcription factor, Myc is manufactured when the cell is stimulated by growth factors to divide, it to binds to DNA activating genes that cause persistent expression of Myc protein even in the absence of growth factors resulting in inappropriate proliferation.

Name and describe two common suppressor genes:

TGF-beta recepors - TGF Beta is a molecule which stops the growth of cells - in some colon cancers a surface receptor for surface B due to inactivation of the gene coding for it - in a similar fashion some cancers discard the p15 gene which responds to TGF B by blocking the cells progress through the growth cycle.

What are the three types of DNA repair?

Mismatch Repair, Nucleotide Excision Repair, Recombination Repair (defects in any lead to much greater risk of genome damage and cancer)

Name a cancer gene associated with a defect in DNA repair:

BRCA1 and BRCA2 - mutations in these genes predispose to early onset breast cancer.

Name a cancer gene mutations in which are associated with avoidance of apoptosis:

p53 - is normally critical in triggering apoptosis of cell is damaged (works by inducing transcription of bax which accelerates cell death by opposing bcl-2, a gene which protects from apoptosis) . Inactivation of p53 can cause cells to evade apoptosis, as can excessive production of BCL2