Radiotherapy-Induced Carcinogenesis and Leukemogenesis: Mechanisms and Quantitative Modeling

  • David J. Brenner
  • Igor Shuryak
  • Rainer K. Sachs
Chapter
Part of the Medical Radiology book series (MEDRAD)

Abstract

Biologically-based modeling of spontaneous and radiation-induced carcinogenesis has a history spanning several decades. Such models are important conceptual and quantitative tools, particularly useful whenever cancer risks must be estimated under exposure situations for which no data yet exist, e.g., for novel and prospective radiotherapy protocols. Direct extrapolation from existing data is often not possible due to complex differences between the data sets, but quantitative models can accommodate such extrapolation. Many carcinogenesis models can be characterized as short-term, in that they focus on those processes occurring during and shortly after irradiation. The main advantage of this class of models is that they provide a detailed initial dose response for short-term endpoints which are used as surrogates for carcinogenesis. The main disadvantage is that the possibly substantial modulations of the magnitude and shape of this initial dose response during the lengthy period between irradiation and manifestation of typical solid tumors are not considered. In contrast with the short-term models, another class of biologically-motivated models can be characterized as long-term, in the sense that they track carcinogenesis mechanisms throughout the entire human life span. The main advantages of long-term models are: (1) modulation of the radiation dose response during the long latency period between exposure and diagnosis of cancer is included; and (2) extensive data on spontaneous cancers can be used to help determine the adjustable parameters needed to estimate cancer risks. The main disadvantage is that the early radiation response is typically treated in a less-mechanistic manner than in the short-term models. Here we review some short- and long-term model examples and the carcinogenesis mechanisms which they incorporate. We also discuss an example of unification of both model classes, focusing on application of such formalisms for quantifying radiotherapy-induced second cancer risks.

References

  1. Almog N, Henke V, Flores L et al (2006) Prolonged dormancy of human liposarcoma is associated with impaired tumor angiogenesis. Faseb J 20:947–949PubMedCrossRefGoogle Scholar
  2. Anonymous (2004) Cancer survivors: living longer, and now, better. Lancet 364:2153–2154Google Scholar
  3. Armitage P (1985) Multistage models of carcinogenesis. Environ Health Perspect 63:195–201PubMedCrossRefGoogle Scholar
  4. Armitage P, Doll R (1954) The age distribution of cancer and a multi-stage theory of carcinogenesis. Br J Cancer VIII:1–12Google Scholar
  5. BEIR VII Report, Phase 2 (2005) Health risks from exposure to low levels of ionizing radiation. The National Academic Press, WashingtonGoogle Scholar
  6. Bennett WR, Crew TE, Slack JM et al (2003) Structural-proliferative units and organ growth: effects of insulin-like growth factor 2 on the growth of colon and skin. Development 130:1079–1088PubMedCrossRefGoogle Scholar
  7. Bennett J, Little MP, Richardson S (2004) Flexible dose-response models for Japanese atomic bomb survivor data: Bayesian estimation and prediction of cancer risk. Radiat Environ Biophys 43:233–245PubMedCrossRefGoogle Scholar
  8. Bockmuhl U, Petersen I (2002) DNA ploidy and chromosomal alterations in head and neck squamous cell carcinoma. Virchows Arch 441:541–550PubMedCrossRefGoogle Scholar
  9. Boice JD Jr, Blettner M, Kleinerman RA et al (1987) Radiation dose and leukemia risk in patients treated for cancer of the cervix. J Natl Cancer Inst 79:1295–1311PubMedGoogle Scholar
  10. Boice JD Jr, Engholm G, Kleinerman RA et al (1988) Radiation dose and second cancer risk in patients treated for cancer of the cervix. Radiat Res 116:3–55PubMedCrossRefGoogle Scholar
  11. Borthwick DW, Shahbazian M, Krantz QT et al (2001) Evidence for stem-cell niches in the tracheal epithelium. Am J Respir Cell Mol Biol 24:662–670PubMedCrossRefGoogle Scholar
  12. Brash DE (2006) Roles of the transcription factor p53 in keratinocyte carcinomas. Br J Dermatol 154(Suppl 1):8–10PubMedCrossRefGoogle Scholar
  13. Brash DE, Zhang W, Grossman D et al (2005) Colonization of adjacent stem cell compartments by mutant keratinocytes. Semin Cancer Biol 15:97–102PubMedCrossRefGoogle Scholar
  14. Brem SS, Gullino PM, Medina D (1977) Angiogenesis: a marker for neoplastic transformation of mammary papillary hyperplasia. Science 195:880–882PubMedCrossRefGoogle Scholar
  15. Brenner DJ, Hahnfeldt P, Amundson SA et al (1996) Interpretation of inverse dose-rate effects for mutagenesis by sparsely ionizing radiation. Int J Radiat Biol 70:447–458PubMedCrossRefGoogle Scholar
  16. Brenner DJ, Curtis RE, Hall EJ et al (2000) Second malignancies in prostate carcinoma patients after radiotherapy compared with surgery. Cancer 88:398–406PubMedCrossRefGoogle Scholar
  17. Brenner DJ, Shuryak I, Russo S et al (2007) Reducing second breast cancers: a potential role for prophylactic mammary irradiation. J Clin Oncol 25:4868–4872PubMedCrossRefGoogle Scholar
  18. Brunet A, Rando TA (2007) Ageing: from stem to stern. Nature 449:288–291PubMedCrossRefGoogle Scholar
  19. Calabrese P, Tavare S, Shibata D (2004) Pretumor progression: clonal evolution of human stem cell populations. Am J Pathol 164:1337–1346PubMedCrossRefGoogle Scholar
  20. Carlson ME, Conboy IM (2007) Loss of stem cell regenerative capacity within aged niches. Aging Cell 6:371–382PubMedCrossRefGoogle Scholar
  21. Chaturvedi AK, Engels EA, Gilbert ES et al (2007) Second cancers among 104,760 survivors of cervical cancer: evaluation of long-term risk. J Natl Cancer Inst 99:1634–1643PubMedCrossRefGoogle Scholar
  22. Cook PJ, Doll R, Fellingham SA (1969) A mathematical model for the age distribution of cancer in man. Int J Cancer 4:93–112PubMedCrossRefGoogle Scholar
  23. Croizat H, Frindel E, Tubiana M (1980) The effect of partial body irradiation on haemopoietic stem cell migration. Cell Tissue Kinet 13:319–325PubMedGoogle Scholar
  24. Curtis SB (1986) Lethal and potentially lethal lesions induced by radiation—a unified repair model. Radiat Res 106:252–270PubMedCrossRefGoogle Scholar
  25. Curtis RE, Boice JD Jr, Stovall M et al (1994) Relationship of leukemia risk to radiation dose following cancer of the uterine corpus. J Natl Cancer Inst 86:1315–1324PubMedCrossRefGoogle Scholar
  26. Curtis SB, Luebeck EG, Hazelton WD et al (2001) The role of promotion in carcinogenesis from protracted high-LET exposure. Phys Med 17(Suppl 1):157–160PubMedGoogle Scholar
  27. Curtis R, Freedman D, Ron E et al (2006) New malignancies among cancer survivors: SEER Cancer Registries, 1973–2000. National Cancer Institute, BethesdaGoogle Scholar
  28. Dale RG (1986) The application of the linear-quadratic model to fractionated radiotherapy when there is incomplete normal tissue recovery between fractions, and possible implications for treatments involving multiple fractions per day. Br J Radiol 59:919–927PubMedCrossRefGoogle Scholar
  29. Dasu A, Toma-Dasu I, Olofsson J et al (2005) The use of risk estimation models for the induction of secondary cancers following radiotherapy. Acta Oncol 44:339–347PubMedCrossRefGoogle Scholar
  30. Feitelson MA, Pan J, Lian Z (2004) Early molecular and genetic determinants of primary liver malignancy. Surg Clin North Am 84:339–354PubMedCrossRefGoogle Scholar
  31. Finley JC, Reid BJ, Odze RD et al (2006) Chromosomal instability in Barrett’s esophagus is related to telomere shortening. Cancer Epidemiol Biomarkers Prev 15:1451–1457PubMedCrossRefGoogle Scholar
  32. Fliedner TM (1998) The role of blood stem cells in hematopoietic cell renewal. Stem Cells 16(Suppl 1):13–29PubMedGoogle Scholar
  33. Fliedner TM, Graessle D, Paulsen C et al (2002) Structure and function of bone marrow hemopoiesis: mechanisms of response to ionizing radiation exposure. Cancer Biother Radiopharm 17:405–426PubMedCrossRefGoogle Scholar
  34. Fuchs E, Tumbar T, Guasch G (2004) Socializing with the neighbors: stem cells and their niche. Cell 116:769–778PubMedCrossRefGoogle Scholar
  35. Ghazizadeh S, Taichman LB (2005) Organization of stem cells and their progeny in human epidermis. J Invest Dermatol 124:367–372PubMedCrossRefGoogle Scholar
  36. Gray LH (1957) Radiobiology and cancer. Nature 179:991–994PubMedCrossRefGoogle Scholar
  37. Hahnfeldt P, Hlatky L (1996) Resensitization due to redistribution of cells in the phases of the cell cycle during arbitrary radiation protocols. Radiat Res 145:134–143PubMedCrossRefGoogle Scholar
  38. Hahnfeldt P, Hlatky L (1998) Cell resensitization during protracted dosing of heterogeneous cell populations. Radiat Res 150:681–687PubMedCrossRefGoogle Scholar
  39. Hall EJ, Wuu CS (2003) Radiation-induced second cancers: the impact of 3D-CRT and IMRT. Int J Radiat Oncol Biol Phys 56:83–88PubMedCrossRefGoogle Scholar
  40. Hanks GE (1964) In vivo migration of colony-forming units from shielded bone marrow in the irradiated mouse. Nature 203:1393–1395PubMedCrossRefGoogle Scholar
  41. Harding C, Pompei F, Lee EE et al (2008) Cancer suppression at old age. Cancer Res 68:4465–4478PubMedCrossRefGoogle Scholar
  42. Heidenreich WF, Hoogenveen R (2001) Limits of applicability for the deterministic approximation of the two-step clonal expansion model. Risk Anal 21:103–105PubMedCrossRefGoogle Scholar
  43. Heidenreich WF, Paretzke HG (2001) The two-stage clonal expansion model as an example of a biologically based model of radiation-induced cancer. Radiat Res 156:678–681PubMedCrossRefGoogle Scholar
  44. Heidenreich WF, Jacob P, Paretzke HG et al (1999) Two-step model for the risk of fatal and incidental lung tumors in rats exposed to radon. Radiat Res 151:209–217PubMedCrossRefGoogle Scholar
  45. Heidenreich WF, Luebeck EG, Hazelton WD et al (2002) Multistage models and the incidence of cancer in the cohort of atomic bomb survivors. Radiat Res 158:607–614PubMedCrossRefGoogle Scholar
  46. Heidenreich WF, Cullings HM, Funamoto S et al (2007) Promoting action of radiation in the atomic bomb survivor carcinogenesis data? Radiat Res 168:750–756PubMedCrossRefGoogle Scholar
  47. Hlatky L, Hahnfeldt P, Tsionou C et al (1996) Vascular endothelial growth factor: environmental controls and effects in angiogenesis. Br J Cancer Suppl 27:S151–S156PubMedGoogle Scholar
  48. Hodgson DC, Koh ES, Tran TH et al (2007) Individualized estimates of second cancer risks after contemporary radiation therapy for Hodgkin lymphoma. Cancer 110:2576–2586PubMedCrossRefGoogle Scholar
  49. Hofmann W, Crawford-Brown DJ, Fakir H et al (2006) Modeling lung cancer incidence in rats following exposure to radon progeny. Radiat Prot Dosimetry 122:345–348PubMedCrossRefGoogle Scholar
  50. Inskip PD, Kleinerman RA, Stovall M et al (1993) Leukemia, lymphoma, and multiple myeloma after pelvic radiotherapy for benign disease. Radiat Res 135:108–124PubMedCrossRefGoogle Scholar
  51. Ivanov VK, Gorski AI, Tsyb AF et al (2004) Solid cancer incidence among the Chernobyl emergency workers residing in Russia: estimation of radiation risks. Radiat Environ Biophys 43:35–42PubMedCrossRefGoogle Scholar
  52. Knudson AG Jr (1971) Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A 68:820–823PubMedCrossRefGoogle Scholar
  53. Koh ES, Tran TH, Heydarian M et al (2007) A comparison of mantle versus involved-field radiotherapy for Hodgkin’s lymphoma: reduction in normal tissue dose and second cancer risk. Radiat Oncol 2:13PubMedCrossRefGoogle Scholar
  54. Kohle C, Schwarz M, Bock KW (2008) Promotion of hepatocarcinogenesis in humans and animal models. Arch Toxicol 82:623–631PubMedCrossRefGoogle Scholar
  55. Komarova NL, Cheng P (2006) Epithelial tissue architecture protects against cancer. Math Biosci 200:90–117PubMedCrossRefGoogle Scholar
  56. Kopp-Schneider A, Portier CJ (1991) Distinguishing between models of carcinogenesis: the role of clonal expansion. Fundam Appl Toxicol 17:601–613PubMedCrossRefGoogle Scholar
  57. Lange CS, Mayer PJ, Reddy NM (1997) Tests of the double-strand break, lethal-potentially lethal and repair-misrepair models for mammalian cell survival using data for survival as a function of delayed-plating interval for log-phase Chinese hamster V79 cells. Radiat Res 148:285–292PubMedCrossRefGoogle Scholar
  58. Leedham SJ, Wright NA (2008) Expansion of a mutated clone—from stem cell to tumour. J Clin Pathol 61(2):164–171 Google Scholar
  59. Leedham SJ, Schier S, Thliveris AT et al (2005) From gene mutations to tumours–stem cells in gastrointestinal carcinogenesis. Cell Prolif 38:387–405PubMedCrossRefGoogle Scholar
  60. Li L, Xie T (2005) Stem cell niche: structure and function. Annu Rev Cell Dev Biol 21:605–631PubMedCrossRefGoogle Scholar
  61. Lindsay KA, Wheldon EG, Deehan C et al (2001) Radiation carcinogenesis modelling for risk of treatment-related second tumours following radiotherapy. Br J Radiol 74:529–536PubMedGoogle Scholar
  62. Little MP (2001) Comparison of the risks of cancer incidence and mortality following radiation therapy for benign and malignant disease with the cancer risks observed in the Japanese A-bomb survivors. Int J Radiat Biol 77:431–464PubMedCrossRefGoogle Scholar
  63. Little MP (2007) A multi-compartment cell repopulation model allowing for inter-compartmental migration following radiation exposure, applied to leukaemia. J Theor Biol 245:83–97PubMedCrossRefGoogle Scholar
  64. Little MP, Li G (2007) Stochastic modelling of colon cancer: is there a role for genomic instability? Carcinogenesis 28:479–487PubMedCrossRefGoogle Scholar
  65. Little MP, Wright EG (2003) A stochastic carcinogenesis model incorporating genomic instability fitted to colon cancer data. Math Biosci 183:111–134PubMedCrossRefGoogle Scholar
  66. Little MP, Weiss HA, Boice JD Jr et al (1999) Risks of leukemia in Japanese atomic bomb survivors, in women treated for cervical cancer, and in patients treated for ankylosing spondylitis. Radiat Res 152:280–292PubMedCrossRefGoogle Scholar
  67. Luebeck EG, Hazelton WD (2002) Multistage carcinogenesis and radiation. J Radiol Prot 22:A43–A49PubMedCrossRefGoogle Scholar
  68. Luebeck EG, Moolgavkar SH (2002) Multistage carcinogenesis and the incidence of colorectal cancer. Proc Natl Acad Sci U S A 99:15095–15100PubMedCrossRefGoogle Scholar
  69. Maley CC (2007) Multistage carcinogenesis in Barrett’s esophagus. Cancer Lett 245:22–32PubMedCrossRefGoogle Scholar
  70. Maley CC, Reid BJ (2005) Natural selection in neoplastic progression of Barrett’s esophagus. Semin Cancer Biol 15:474–483PubMedCrossRefGoogle Scholar
  71. McDonald SA, Preston SL, Greaves LC et al (2006) Clonal expansion in the human gut: mitochondrial DNA mutations show us the way. Cell Cycle 5:808–811PubMedCrossRefGoogle Scholar
  72. Mebust M, Crawford-Brown D, Hofmann W et al (2002) Testing extrapolation of a biologically based exposure-response model from in vitro to in vivo conditions. Regul Toxicol Pharmacol 35:72–79PubMedCrossRefGoogle Scholar
  73. Meza R, Jeon J, Moolgavkar SH et al (2008) Age-specific incidence of cancer: phases, transitions, and biological implications. Proc Natl Acad Sci U S A 105:16284–16289PubMedCrossRefGoogle Scholar
  74. Michor F, Iwasa Y, Komarova NL et al (2003a) Local regulation of homeostasis favors chromosomal instability. Curr Biol 13:581–584PubMedCrossRefGoogle Scholar
  75. Michor F, Frank SA, May RM et al (2003b) Somatic selection for and against cancer. J Theor Biol 225:377–382PubMedCrossRefGoogle Scholar
  76. Michor F, Iwasa Y, Rajagopalan H et al (2004) Linear model of colon cancer initiation. Cell Cycle 3:358–362PubMedCrossRefGoogle Scholar
  77. Michor F, Iwasa Y, Lengauer C et al (2005) Dynamics of colorectal cancer. Semin Cancer Biol 15:484–493PubMedCrossRefGoogle Scholar
  78. Midorikawa Y, Makuuchi M, Tang W et al (2007) Microarray-based analysis for hepatocellular carcinoma: from gene expression profiling to new challenges. World J Gastroenterol 13:1487–1492PubMedGoogle Scholar
  79. Moolgavkar SH (1978) The multistage theory of carcinogenesis and the age distribution of cancer in man. J Natl Cancer Inst 61:49–52PubMedGoogle Scholar
  80. Moolgavkar S (1980) Multistage models for carcinogenesis. J Natl Cancer Inst 65:215–216PubMedGoogle Scholar
  81. Moolgavkar SH (1983) Model for human carcinogenesis: action of environmental agents. Environ Health Perspect 50:285–291PubMedCrossRefGoogle Scholar
  82. Moolgavkar SH (1986) Carcinogenesis modeling: from molecular biology to epidemiology. Annu Rev Public Health 7:151–169PubMedCrossRefGoogle Scholar
  83. Moolgavkar SH, Knudson AG Jr (1981) Mutation and cancer: a model for human carcinogenesis. J Natl Cancer Inst 66:1037–1052PubMedGoogle Scholar
  84. Naumov GN, Bender E, Zurakowski D et al (2006) A model of human tumor dormancy: an angiogenic switch from the nonangiogenic phenotype. J Natl Cancer Inst 98:316–325PubMedCrossRefGoogle Scholar
  85. NCRP Report 136 (2001) Evaluation of the linear-nonthreshold dose-response model for ionizing radiation. The National Academic Press, WashingtonGoogle Scholar
  86. Neglia JP, Robison LL, Stovall M et al (2006) New primary neoplasms of the central nervous system in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Natl Cancer Inst 98:1528–1537PubMedCrossRefGoogle Scholar
  87. Nguyen LN, Ang KK (2002) Radiotherapy for cancer of the head and neck: altered fractionation regimens. Lancet Oncol 3:693–701PubMedCrossRefGoogle Scholar
  88. Nilsson P, Thames HD, Joiner MC (1990) A generalized formulation of the ‘incomplete-repair’ model for cell survival and tissue response to fractionated low dose-rate irradiation. Int J Radiat Biol 57:127–142PubMedCrossRefGoogle Scholar
  89. Nishimura M, Furumoto H, Kato T et al (2000) Microsatellite instability is a late event in the carcinogenesis of uterine cervical cancer. Gynecol Oncol 79:201–206PubMedCrossRefGoogle Scholar
  90. Nordling CO (1953) A new theory on the cancer inducing mechanism. Br J Cancer 7:68–72PubMedCrossRefGoogle Scholar
  91. Nowak MA, Komarova NL, Sengupta A et al (2002) The role of chromosomal instability in tumor initiation. Proc Natl Acad Sci U S A 99:16226–16231PubMedCrossRefGoogle Scholar
  92. Nowak MA, Michor F, Iwasa Y (2006) Genetic instability and clonal expansion. J Theor Biol 241:26–32PubMedCrossRefGoogle Scholar
  93. Ohtaki M, Niwa O (2001) A mathematical model of radiation carcinogenesis with induction of genomic instability and cell death. Radiat Res 156:672–677PubMedCrossRefGoogle Scholar
  94. Ottolenghi A, Ballarini F, Merzagora M (1999) Modelling radiation-induced biological lesions: from initial energy depositions to chromosome aberrations. Radiat Environ Biophys 38:1–13PubMedCrossRefGoogle Scholar
  95. Perez-Ordonez B, Beauchemin M, Jordan RC (2006) Molecular biology of squamous cell carcinoma of the head and neck. J Clin Pathol 59:445–453PubMedCrossRefGoogle Scholar
  96. Pierce DA, Mendelsohn ML (1999) A model for radiation-related cancer suggested by atomic bomb survivor data. Radiat Res 152:642–654PubMedCrossRefGoogle Scholar
  97. Pierce DA, Vaeth M (2003) Age-time patterns of cancer to be anticipated from exposure to general mutagens. Biostatistics 4:231–248PubMedCrossRefGoogle Scholar
  98. Pompei F, Wilson R (2002) A quantitative model of cellular senescence influence on cancer and longevity. Toxicol Ind Health 18:365–376PubMedCrossRefGoogle Scholar
  99. Pompei F, Polkanov M, Wilson R (2001) Age distribution of cancer in mice: the incidence turnover at old age. Toxicol Ind Health 17:7–16PubMedCrossRefGoogle Scholar
  100. Potten CS, Booth C (2002) Keratinocyte stem cells: a commentary. J Invest Dermatol 119:888–899PubMedCrossRefGoogle Scholar
  101. Radivoyevitch T, Kozubek S, Sachs RK (2001) Biologically based risk estimation for radiation-induced CML. Inferences from BCR and ABL geometric distributions. Radiat Environ Biophys 40:1–9PubMedCrossRefGoogle Scholar
  102. Ritter G, Wilson R, Pompei F et al (2003) The multistage model of cancer development: some implications. Toxicol Ind Health 19:125–145PubMedCrossRefGoogle Scholar
  103. Ron E (2006) Childhood cancer—treatment at a cost. J Natl Cancer Inst 98:1510–1511PubMedCrossRefGoogle Scholar
  104. Ronckers CM, Sigurdson AJ, Stovall M et al (2006) Thyroid cancer in childhood cancer survivors: a detailed evaluation of radiation dose response and its modifiers. Radiat Res 166:618–628PubMedCrossRefGoogle Scholar
  105. Rossi HH, Kellerer AM (1986) The dose rate dependence of oncogenic transformation by neutrons may be due to variation of response during the cell cycle. Int J Radiat Biol Relat Stud Phys Chem Med 50:353–361PubMedCrossRefGoogle Scholar
  106. Rusyn I, Peters JM, Cunningham ML (2006) Modes of action and species-specific effects of di-(2-ethylhexyl)phthalate in the liver. Crit Rev Toxicol 36:459–479PubMedCrossRefGoogle Scholar
  107. Sachs RK, Brenner DJ (2005) Solid tumor risks after high doses of ionizing radiation. Proc Natl Acad Sci U S A 102:13040–13045PubMedCrossRefGoogle Scholar
  108. Sachs RK, Chan M, Hlatky L et al (2005) Modeling intercellular interactions during carcinogenesis. Radiat Res 164:324–331PubMedCrossRefGoogle Scholar
  109. Sachs RK, Shuryak I, Brenner D et al (2007) Second cancers after fractionated radiotherapy: stochastic population dynamics effects. J Theor Biol 249:518–531PubMedCrossRefGoogle Scholar
  110. Schneider U, Kaser-Hotz B (2005) Radiation risk estimates after radiotherapy: application of the organ equivalent dose concept to plateau dose-response relationships. Radiat Environ Biophys 44:235–239PubMedCrossRefGoogle Scholar
  111. Schneider U, Walsh L (2008) Cancer risk estimates from the combined Japanese A-bomb and Hodgkin cohorts for doses relevant to radiotherapy. Radiat Environ Biophys 47:253–263PubMedCrossRefGoogle Scholar
  112. Schollnberger H, Mitchel RE, Crawford-Brown DJ et al (2002) Nonlinear dose-response relationships and inducible cellular defence mechanisms. J Radiol Prot 22:A21–A25PubMedCrossRefGoogle Scholar
  113. Sharpless NE, DePinho RA (2007) How stem cells age and why this makes us grow old. Nat Rev Mol Cell Biol 8:703–713PubMedCrossRefGoogle Scholar
  114. Shaw IC, Jones HB (1994) Mechanisms of non-genotoxic carcinogenesis. Trends Pharmacol Sci 15:89–93PubMedCrossRefGoogle Scholar
  115. Shuryak I, Sachs RK, Hlatky L et al (2006) Radiation-induced leukemia at doses relevant to radiation therapy: modeling mechanisms and estimating risks. J Natl Cancer Inst 98:1794–1806PubMedCrossRefGoogle Scholar
  116. Shuryak I, Hahnfeldt P, Hlatky L, Sachs RK, Brenner DJ (2009a) A new view of radiation-induced cancer: integrating short- and long-term processes. Part I: approach. Radiat Environ Biophys 48(3):263–274 (Erratum in: Radiat Environ Biophys 50(4):607–608)Google Scholar
  117. Shuryak I, Hahnfeldt P, Hlatky L, Sachs RK, Brenner DJ (2009b) A new view of radiation-induced cancer: integrating short- and long-term processes. Part II: second cancer risk estimation. Radiat Environ Biophys 48(3):275–286 (Erratum in: Radiat Environ Biophys 50(4):607–608)Google Scholar
  118. Slack JM (2000) Stem cells in epithelial tissues. Science 287:1431–1433PubMedCrossRefGoogle Scholar
  119. Sontag W (1997) A discrete cell survival model including repair after high dose-rate of ionizing radiation. Int J Radiat Biol 71:129–144PubMedCrossRefGoogle Scholar
  120. Spiess PE, Czerniak B (2006) Dual-track pathway of bladder carcinogenesis: practical implications. Arch Pathol Lab Med 130:844–852PubMedGoogle Scholar
  121. Stewart RD (2001) Two-lesion kinetic model of double-strand break rejoining and cell killing. Radiat Res 156:365–378PubMedCrossRefGoogle Scholar
  122. Tahara E (2004) Genetic pathways of two types of gastric cancer. IARC Sci Publ 157:327–349PubMedGoogle Scholar
  123. Tamura G (2006) Alterations of tumor suppressor and tumor-related genes in the development and progression of gastric cancer. World J Gastroenterol 12:192–198PubMedGoogle Scholar
  124. Thames HD (1985) An ‘incomplete-repair’ model for survival after fractionated and continuous irradiations. Int J Radiat Biol Relat Stud Phys Chem Med 47:319–339PubMedCrossRefGoogle Scholar
  125. Thomlinson RH, Gray LH (1955) The histological structure of some human lung cancers and the possible implications for radiotherapy. Br J Cancer 9:539–549PubMedCrossRefGoogle Scholar
  126. Tobias CA (1985) The repair-misrepair model in radiobiology: comparison to other models. Radiat Res Suppl 8:S77–S95PubMedCrossRefGoogle Scholar
  127. Travis LB, Andersson M, Gospodarowicz M et al (2000) Treatment-associated leukemia following testicular cancer. J Natl Cancer Inst 92:1165–1171PubMedCrossRefGoogle Scholar
  128. Travis LB, Gospodarowicz M, Curtis RE et al (2002) Lung cancer following chemotherapy and radiotherapy for Hodgkin’s disease. J Natl Cancer Inst 94:182–192PubMedCrossRefGoogle Scholar
  129. Travis LB, Hill DA, Dores GM et al (2003) Breast cancer following radiotherapy and chemotherapy among young women with Hodgkin disease. JAMA 290:465–475PubMedCrossRefGoogle Scholar
  130. Trosko JE (2006) From adult stem cells to cancer stem cells: Oct-4 Gene, cell–cell communication, and hormones during tumor promotion. Ann N Y Acad Sci 1089:36–58PubMedCrossRefGoogle Scholar
  131. Upton AC (2003) The state of the art in the 1990’s: NCRP Report No. 136 on the scientific bases for linearity in the dose-response relationship for ionizing radiation. Health Phys 85:15–22PubMedCrossRefGoogle Scholar
  132. Weiss HA, Darby SC, Fearn T et al (1995) Leukemia mortality after X-ray treatment for ankylosing spondylitis. Radiat Res 142:1–11PubMedCrossRefGoogle Scholar
  133. Wheldon EG, Lindsay KA, Wheldon TE (2000) The dose-response relationship for cancer incidence in a two-stage radiation carcinogenesis model incorporating cellular repopulation. Int J Radiat Biol 76:699–710PubMedCrossRefGoogle Scholar
  134. Yakovlev A, Polig E (1996) A diversity of responses displayed by a stochastic model of radiation carcinogenesis allowing for cell death. Math Biosci 132:1–33PubMedCrossRefGoogle Scholar
  135. Yamasaki H, Mesnil M, Nakazawa H (1992) Interaction and distinction of genotoxic and non-genotoxic events in carcinogenesis. Toxicol Lett 64–65 Spec No:597–604Google Scholar
  136. Zaider M, Wuu CS (1995) The effects of sublethal damage recovery and cell cycle progression on the survival probability of cells exposed to radioactive sources. Br J Radiol 68:58–63PubMedCrossRefGoogle Scholar
  137. Zelefsky MJ, Fuks Z, Hunt M et al (2002) High-dose intensity modulated radiation therapy for prostate cancer: early toxicity and biochemical outcome in 772 patients. Int J Radiat Oncol Biol Phys 53:1111–1116PubMedCrossRefGoogle Scholar
  138. Zhang W, Remenyik E, Zelterman D et al (2001) Escaping the stem cell compartment: sustained UVB exposure allows p53-mutant keratinocytes to colonize adjacent epidermal proliferating units without incurring additional mutations. Proc Natl Acad Sci U S A 98:13948–13953PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • David J. Brenner
    • 1
  • Igor Shuryak
    • 1
  • Rainer K. Sachs
    • 2
  1. 1.Center for Radiological ResearchColumbia University Medical CenterNew YorkUSA
  2. 2.Departments of Mathematics and PhysicsUniversity of CaliforniaBerkeleyUSA

Personalised recommendations