Cellular Defenses Against Radiation-Induced Carcinogenesis:

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Major classes of DNA damage: Strand breaks Base damage Crosslinks DSB SSB Oxydative Alkylation Bulk adducts Interstrand Intrastrand DNA-protein NCI REB <strong>Radiation</strong> Epidemiology Course, May 14, 2007 TJJ
Major DNA repair pathways: • Non-homologous end joining (NHEJ) • Base Excision Repair (BER) • Nucleotide Excision Repair (NER) • Homologous Recombination Repair • Illegitimate Recombination Repair • Mismatch Repair (MMR) NCI REB <strong>Radiation</strong> Epidemiology Course, May 14, 2007 TJJ
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 and 22: DO DEFECTIVE CHECKPOINTS CAUSE CANC
Page 23 and 24: Radiation-Induced G2 delay in lymph
Page 27 and 28: Rothkamm and Lobrick, PNAS, 2003 NC
Page 29: Somatic Mutation and Cancer Environ
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
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 81 and 82:
NCI REB Radiation Epidemiology Cour
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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:
Page 89 and 90:
NCI REB Radiation Epidemiology Cour
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Veratrum californicum (corn lily) N
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Frank-Kamenetsky et al. J. Biol. 1:
Page 95 and 96:
CONFOUNDERS: AGE SKIN COLOR DOSE NC
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• A disease of accelerated aging.
Page 99 and 100:
Age-Dependent Reactive Oxygen Speci
Page 101 and 102:
SKIN COLOR GENETICS NCI REB Radiati
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Am J Epidemiol 155: 614, 2002 Melan
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Melanocortin 1 Receptor gene (MC1R)
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SKIN COLOR GEOGRAPHY Photograph by
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DOSE NCI REB Radiation Epidemiology
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National Geographic Magazine April
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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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