Cellular Defenses Against Radiation-Induced Carcinogenesis:

More documents

Recommendations

Info

BCC itself is a risk factor for other cancers Cancer 100:1, 2004 NCI REB Radiation Epidemiology Course, May 14, 2007 TJJ
Radiation as a Model Carcinogen: • Known to be a human carcinogen for almost 100 years. • Strong epidemiological evidence shows clear dose response. • High dose risks known with reasonable precision/accuracy. • Low dose risks are highly uncertain and model dependent. • All tissues believed to be at risk. • Some risk incurred at all dose levels (i.e. no threshold). • Dosimetry is very good. (What is a “pack-year” anyway!) • All individuals in a population are exposed to some degree. • Range of exposures within a population can be quite broad. • Direct interaction with the target of carcinogenesis, and confines the problem to downstream of DNA damage. • Major cellular protective molecular mechanisms known in some degree of detail (e.g. DNA repair and cell cycle arrest). • Radiation is a relatively weak carcinogen (room for genetic enhancement). NCI REB Radiation 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 7 and 8:
Page 9 and 10:
Cancer cells “evolve” into a hi
Page 11 and 12:
WHY CHECKPOINTS Fidelity of cell di
Page 13 and 14:
Page 15 and 16:
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 25 and 26:
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 33 and 34:
Page 35 and 36:
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 59 and 60:
Page 61 and 62:
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
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 89 and 90: NCI REB Radiation Epidemiology Cour
Page 91 and 92: Veratrum californicum (corn lily) N
Page 93 and 94: Frank-Kamenetsky et al. J. Biol. 1:
Page 95 and 96: CONFOUNDERS: AGE SKIN COLOR DOSE NC
Page 97 and 98: • A disease of accelerated aging.
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: RR for XP patients by age 8000 8000
show all

Cellular Defenses Against Radiation-Induced Carcinogenesis:

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?