Multi-Hit Model,”Cancer is a disease of aging. It’s not a disease that affects the young people (rare)bottom graph: how many days during the life of the mouse it’ll go through while tumor freeMyc mice relatively tumor free after 120 days, then gradual decline in # of tumor free individualsCompared to Ras, finding that mice that harbor Ras oncogene start acquiring tumors much, much earlierIf cross two strains, now have mice that have both oncogenes. Ras operating much further upstream than Myc. When put together, get synergistic effect, causing rapid onset of tumorigenesis

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“You’re performing the Ames test on two known carcinogens; Benzo(a)pyrene (BaP) and methyl nitrosourea (MNU). If you treat His-Salmonella with MNU, you generate many His+ colonies. In contrast, if you treat His auxotrophic Salmonella with BaP, you generate no His prototrophs. However, if you first incubate the BaP with a liver extract before adding it to the His auxotroph Salmonella, you generate many His prototrophs. How do BaP and MNU differ?”

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Benzo(a)pyrene,”when you ingest it, will have a hard time excreting it b/c not water solubleepoxide intermediate reacts very strongly w/ Guanine (makes covalent bond w/ amino group)no enzyme to cleave bondModified Guanine has distorted structure in DNA double helix–if not removed before DNA replication takes place (p53’s job), it’s distortedDNA polymerase will not pair it with C-it will pair it with A (G-A mismatch)Cell keeps G and converts opposite T to C (which is good, but doesn’t always happen)Some cells throw out modified G and replace it with T. Original G on DNA sequence, converted to T(A-T basepair

Average Rating 0 out of 5 stars. 0 votes.You must log in to submit a review.Benzo(a)pyrene,”when you ingest it, will[…]

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Clonal Expansion,”explains overwhelming majority of cancersinitial single event happens w/ initial mutation which allows one cell in all cohorts to have proliferative damagecould be loss of tumor suppressor (eliminate DNA damage checkpoints, other DNA mutations can occur)cell not going to proliferate all of its progenetersGoing to get a population of cells that expand and harbor the initial mutation (proliferating) and going through DNA replicationIf they acquire subsequent mutation, that can also be selectedA type of second mutation that you can select for here might be mutation that allows cancer cell to escape immune surveillance (cells now have selective advantage)out of initial population, now have cohort of cellsmall # of cells now requires 2nd mutation, now acquiring 3rd mutationdeprived of oxygen; altered metabolism (cells basically have Raf and Ras mutations have increased GLUT1 transporters, able to import glucose more readily)Looking at 100s of mutations, and comparing DNA sequence of normal cell, and all cells in intermediate states in progression

Average Rating 0 out of 5 stars. 0 votes.You must log in to submit a review.Clonal Expansion,”explains overwhelming majority of[…]

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