Cellular Defenses Against Radiation-Induced Carcinogenesis:

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Evidence for the role of the G2-M checkpoint in cancer is weaker: 1. Cells from A-T patients undergo reduced G2-M arrest in response to DNA damage. 2. Cancer cell lines often have reduced G2-M arrest. 3. Some cancer cells have altered expression of cyclins A, B, and CDC2. NCI REB Radiation Epidemiology Course, May 14, 2007 TJJ
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Page 1 and 2: Cellular Defenses Against Radiation
Page 3 and 4: GOALS: • Provide an overall descr
Page 5 and 6: NCI REB Radiation Epidemiology Cour
Page 9 and 10: Cancer cells “evolve” into a hi
Page 11 and 12: WHY CHECKPOINTS Fidelity of cell di
Page 17 and 18: Cyclin/CDK complexes seem to be reg
Page 19 and 20: • At least two checkpoints are re
Page 21: DO DEFECTIVE CHECKPOINTS CAUSE CANC
Page 27 and 28: Rothkamm and Lobrick, PNAS, 2003 NC
Page 29 and 30: Somatic Mutation and Cancer Environ
Page 31 and 32: Major DNA repair pathways: • Non-
Page 37 and 38: “… the failure of DNA repair in
Page 39 and 40: T. Lindahl and R.D. Wood, Science 2
Page 41 and 42: NER PATHWAY GENES GENE ALIASES DESC
Page 43 and 44: Mismatch repair associated tumors i
Page 45 and 46: Non-Homologous End Joining (NHEJ) N
Page 47 and 48: Illegitimate Recombination NCI REB
Page 49 and 50: TARGET THEORY NCI REB Radiation Epi
Page 51 and 52: A-T CELL CANCER CELL DEATH NCI REB
Page 53 and 54: OTHER TARGET QUESTIONS: • If DNA
Page 55 and 56: Mutations in Chk2 produce the Li-Fr
Page 57 and 58: CASE STUDY: Finding Molecular Targe
Page 63 and 64: Environmental Causes of BCC • UV
Page 65 and 66: UV DAMAGE TO DNA NCI REB Radiation
Page 67 and 68: NER PATHWAY GENES GENE ALIASES DESC
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Page 71 and 72: For BCC, PTCH may be even a bigger
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Gorlin Syndrome • Nevoid basal ce
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Taipale J and Beachy PA Nature 411:
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PTCH may play a role in cell cycle
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NCI REB Radiation Epidemiology Cour
Page 83 and 84:
Aszterbaum et al. Nature Med. 5:128
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Shh, PTCH, and SUFU mutations produ
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Thomas et al., J. Postgrad Med. 49:
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NCI REB Radiation Epidemiology Cour
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• A disease of accelerated aging.
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National Geographic Magazine April
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Aging genes (I.e. non-DNA repair) A
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RR for XP patients by age 8000 8000
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Radiation as a Model Carcinogen:
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Cellular Defenses Against Radiation-Induced Carcinogenesis:

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