Cellular Defenses Against Radiation-Induced Carcinogenesis:

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AGE The Bare Facts of Aging Photograph by Sarah Leen NCI REB <strong>Radiation</strong> Epidemiology Course, May 14, 2007 National Geographic Magazine, November 2002 TJJ
• A disease of accelerated aging. • Gene (WRN) encodes a helicase (RecQ) involved in DNA repair and DNA replication. • Normal aging may involve decrease in DNA repair. • Scleroderma-like skin changes. WERNER SYNDROME • Increased incidence of malignancy: GI tract, lung, kidney, ovary, breast. 14 y 48 y NCI REB <strong>Radiation</strong> Epidemiology Course, May 14, 2007 TJJ
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Cellular Defenses Against Radiation
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GOALS: • Provide an overall descr
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NCI REB Radiation Epidemiology Cour
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Cancer cells “evolve” into a hi
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WHY CHECKPOINTS Fidelity of cell di
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Cyclin/CDK complexes seem to be reg
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• At least two checkpoints are re
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DO DEFECTIVE CHECKPOINTS CAUSE CANC
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Radiation-Induced G2 delay in lymph
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Rothkamm and Lobrick, PNAS, 2003 NC
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Somatic Mutation and Cancer Environ
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Major DNA repair pathways: • Non-
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“… the failure of DNA repair in
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T. Lindahl and R.D. Wood, Science 2
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NER PATHWAY GENES GENE ALIASES DESC
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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 59 and 60: NCI REB Radiation Epidemiology Cour
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
Page 69 and 70: Skin cancers have unique p53 mutati
Page 71 and 72: For BCC, PTCH may be even a bigger
Page 73 and 74: Gorlin Syndrome • Nevoid basal ce
Page 75 and 76: Verónica Martín, Graciela Carrill
Page 77 and 78: Taipale J and Beachy PA Nature 411:
Page 79 and 80: PTCH may play a role in cell cycle
Page 83 and 84: Aszterbaum et al. Nature Med. 5:128
Page 85 and 86: Shh, PTCH, and SUFU mutations produ
Page 87 and 88: Thomas et al., J. Postgrad Med. 49:
Page 91 and 92: Veratrum californicum (corn lily) N
Page 93 and 94: Frank-Kamenetsky et al. J. Biol. 1:
Page 95: CONFOUNDERS: AGE SKIN COLOR DOSE NC
Page 99 and 100: Age-Dependent Reactive Oxygen Speci
Page 101 and 102: SKIN COLOR GENETICS NCI REB Radiati
Page 103 and 104: Am J Epidemiol 155: 614, 2002 Melan
Page 105 and 106: Melanocortin 1 Receptor gene (MC1R)
Page 107 and 108: SKIN COLOR GEOGRAPHY Photograph by
Page 109 and 110: DOSE NCI REB Radiation Epidemiology
Page 111 and 112: National Geographic Magazine April
Page 113 and 114: Aging genes (I.e. non-DNA repair) A
Page 115 and 116: RR for XP patients by age 8000 8000
Page 117 and 118: Radiation as a Model Carcinogen:
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