Cellular Defenses Against Radiation-Induced Carcinogenesis:

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Nature 422:313, 2003 Cyclopamine inhibits growth of tumors with activated hedgehog pathways. NCI REB <strong>Radiation</strong> Epidemiology Course, May 14, 2007 TJJ
CONFOUNDERS: AGE SKIN COLOR DOSE 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
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 59 and 60: NCI REB Radiation Epidemiology Cour
Page 63 and 64: Environmental Causes of BCC • UV
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Page 71 and 72: For BCC, PTCH may be even a bigger
Page 73 and 74: Gorlin Syndrome • Nevoid basal ce
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Page 83 and 84: Aszterbaum et al. Nature Med. 5:128
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Page 91 and 92: Veratrum californicum (corn lily) N
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Page 97 and 98: • A disease of accelerated aging.
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