Cellular Defenses Against Radiation-Induced Carcinogenesis:

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Aging DNA repair genes DNA repair DNA Damage (cancer) The multiple pathways through which aging can interact in the gene to cancer pathway, makes aging an important confounder that needs to be carefully adjusted for. Epidemiological limitation is that we can only adjust for chronological age and not biological age. NCI REB <strong>Radiation</strong> Epidemiology Course, May 14, 2007 TJJ
SKIN COLOR GENETICS 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
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Non-Homologous End Joining (NHEJ) N
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Illegitimate Recombination NCI REB
Page 49 and 50: TARGET THEORY NCI REB Radiation Epi
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Page 57 and 58: CASE STUDY: Finding Molecular Targe
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Page 63 and 64: Environmental Causes of BCC • UV
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Page 95 and 96: CONFOUNDERS: AGE SKIN COLOR DOSE NC
Page 97 and 98: • A disease of accelerated aging.
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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
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