Radyasyon Biyolojisi, Radyobiyoloji
Özet
Radyasyon biyolojisi, radyasyonun biyolojik sistemler ve canlı dokular üzerindeki karmaşık etkilerini inceleyen bilim dalıdır. İyonlaştırıcı radyasyon, hücre bölünmesi ve büyümesiyle ilgili genetik bilgiyi taşıyan DNA moleküllerini hedef alarak doğrudan veya dolaylı mekanizmalarla hasar meydana getirir. Bu süreçte ortaya çıkan moleküler kırıklar ve serbest radikaller; hücre zarı, endoplazmik retikulum ve mitokondri gibi hayati organellerde yapısal ve işlevsel bozulmalara yol açar. Hücresel düzeydeki en belirgin etkiler; hücre bölünmesinin baskılanması, kromozomal anormallikler ve klonojenik kapasitenin kaybı olarak tanımlanan hücre ölümüdür. Hücrelerin radyasyona karşı en duyarlı olduğu evre mitoz (M) fazı iken, DNA onarım mekanizmalarının en aktif olduğu S fazı en dirençli evredir. Dokuların radyoduyarlılığı mitotik aktivitelerine göre değişir; kemik iliği ve intestinal epitel yüksek duyarlılık gösterirken, kas ve sinir dokuları radyasyona dirençlidir. Kanser tedavisinde radyoterapinin başarısı, tümör kontrol olasılığı ile normal doku komplikasyon olasılığı arasındaki dengeyi ifade eden terapötik pencereye bağlıdır. Tümör mikroçevresi, hipoksi, anjiyogenez ve bağışıklık sisteminden kaçma gibi faktörler radyasyon direncini etkileyen kritik unsurlardır.
Radiation biology explores the complex effects of radiation on biological systems and living tissues. Ionizing radiation targets DNA molecules, which carry genetic information for cell division and growth, causing damage through direct or indirect mechanisms. The resulting molecular breaks and free radicals lead to structural and functional alterations in vital organelles, including the cell membrane, endoplasmic reticulum, and mitochondria. Prominent cellular effects involve the suppression of cell division, chromosomal aberrations, and cell death, defined as the loss of clonogenic capacity. Cells exhibit peak radiosensitivity during the mitosis (M) phase, whereas the S phase remains the most resistant due to highly active DNA repair mechanisms. Tissue radiosensitivity varies by mitotic activity; bone marrow and intestinal epithelium are highly sensitive, while muscle and nerve tissues are radioresistant. The success of radiotherapy in cancer treatment relies on the therapeutic window, representing the balance between tumor control and normal tissue complication probabilities. Factors such as tumor microenvironment, hypoxia, angiogenesis, and immune evasion significantly influence radiation resistance.
Referanslar
Bodansky D (2007) Effects of radiation exposures. In: Bodansky D (ed.) Nuclear energy. Springer, pp 85–121.
Kaul A, Becker D (eds.) (2005) Radiological protection. Springer, pp 5–40.
Wouters BG, Begg AC. Irradiation-induced damage and the DNA damage response. In: Joiner M, Van der Kogel AJ, eds. Basic Clinical Radiobiology. 4th ed. Hodder Arnold; 2009. p.11-26.
Hall EJ, Giaccia AJ. Physics and chemistry of radiation absorption. Radiobiology for the radiologist. 6th ed. Lippincott Williams and Wilkins; 2006. p. 5-15.
Little MP. Cancer after exposure to radiation in the course of treatment for benign and malignant disease. Lancet Oncol 2001;2 (4):212- 20.
Pouget JP, Georgakilas AG, Ravanat JL. Targeted and offtarget (bystander and abscopal) effects of radiation therapy: Redox mechanisms and risk/benefit analysis. Antioxid Redox Signal. 2018;29(15):1447-87.
Pannkuk EL, Laiakis EC, Singh VK, Fornace AJ. Lipidomic signatures of nonhuman primates with radiation-induced hematopoietic syndrome. Sci Rep. 2017;7(1):9777.
Bhattacharya P, Shetake NG, Pandey BN, Kumar A. Receptor tyrosine kinase signaling in cancer radiotherapy and its targeting for tumor radiosensitization. Int J Radiat Biol. 2018;94(7):628-44.
Levine JH, Lin Y, Elowitz MB. Functional roles of pulsing in genetic circuits. Science. 2013;342(6163):1193-200.
Purvis JE, Karhohs KW, Mock C, Batchelor E, Loewer A, Lahav G. p53 dynamics control cell fate. Science. 2012;336(6087):1440-4.
Prevo R, Pirovano G, Puliyadi R, Herbert KJ, RodriguezBerriguete G, O'Docherty A, et al. CDK1 inhibition sensitizes normal cells to DNA damage in a cell cycle dependent manner. Cell Cycle. 2018;17(12):1513-23.
Goitein M (2008) Radiation oncology: a physicist’s eye view. Springer, pp 3–4.
Podgorsak EB (2005) Radiation oncology physics: a handbook for teachers and students. International Atomic Energy Agency, Vienna, pp 485–491.
Belli JA, Dicus GI, Bonte FJ. Radiation response of mammalian tumor cells: 1.Repair of sublethal damage in vivo. J Natl Cancer Inst. 1967; 38: 673-682.
Vermeulen K, Van Bockstaele DR, Berneman ZN. The cell cycle: A review of regulation, deregulation and therapeutic targets in cancer. Cell Prolif. 2003;36(3):131-49.
Howard A, Pelc SR. Nuclear incorporation of P32 as demonstrated by autoradiographs. Exp Cell Res. 1951;2:178–198.
N. Yang, A. M. Sheridan, Cell Cycle, Editor(s): Philip Wexler, Encyclopedia of Toxicology (Third Edition), Academic Press, 2014, pp: 753-758.
Bergonie J, Tribondeau L (1906) Interprétation de quelques résultats de la radiothérapie et essaide fixation d’une technique rationelle. C R Acad Sci 143:983–985.
Awwad HK (2005) Normal tissue radiosensitivity: prediction on deterministic or stochastic basis? J Egypt Natl Canc Inst. 17(4):221–230.
Taner CT. İyonlaştırıcı radyasyonların biyolojik etkileşme mekanizmaları. Türkiye Atom Enerjisi Kurumu (Acant@Taek.Gov.Tr ).
Ercan M. Radyasyonun moleküler düzeydeki etkisi. Erişim: http://194.27.141.99/dosya-depo/ders-notlari/alevmeltem-ercan Radyasyonun Moleküler Düzeydeki Etkisi Doç.Dr. Meltem E.pdf.
Coşkun Ö. İyonize radyasyonun biyolojik etkileri. Teknik Bilimler Dergisi. 2011;1(2):13-7.
Willers H, Held KD (2006) Introduction to clinical radiation biology. Hematol Oncol Clin North Am. 20(1):1–24.
Khan FM. Treatment Planning in Radiation Oncology, 2nd ed. Lippincott Williams and Wilkins, 2007.
Mole RH. Whole body irradiation; radiobiology or medicine? Br J Radiol 1953;26(305): 234-41.
Nobler M.P. The abscopal effect in malignant lymphoma and its relationship to lymphocyte circulation. Radiology. 1969;93(2):410-2.
Demaria S, Ng B, Devitt ML, Babb JS, Kawashima N, Liebes L. et al. Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediated. Int J Radiat Oncol Biol Phys. 2004;58(3):862-70.
Lugade AA, Moran JP, Gerber SA, Rose RC, Frelinger JG, Lord EM. Local radiation therapy of B16 melanoma tumors increases the generation of tumor antigen-specific effector cells that traffic to the tumor. J Immunol. 2005;174(12):7516-23.
Nikitina EY, Gabrilovich DI. Combination of gamma-irradiation and dendritic cell administration induces a potent antitumor response in tumorbearing mice: approach to treatment of advanced stage cancer. Int J Cancer. 2001;94(6):825-33.
Shiraishi K, Ishiwata Y, Nakagawa K, Yokochi S, Taruki C, Akuta T, et al. Enhancement of antitumor radiation efficacy and consistent induction of the abscopal effect in mice by ECI301, an active variant of macrophage inflammatory protein-1 alpha. Clin Cancer Res. 2008;14(4):1159-66.
Takeshima T, Chamoto K, Wakita D, Ohkuri T, Togashi Y, Shirato H, et al. Local radiation therapy inhibits tumor growth through the generation of tumor-specific CTL: its potentiation bycombination with Th1 cell therapy. Cancer Res. 2010;70(7):2697-706.
Dewan MZ, Galloway AE, Kawashima N, Dewyngaert JK, Babb JS, Formenti SC, et al. Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody. Clin Cancer Res. 2009;15(17):5379-88.
Camphausen K, Moses MA, Menard C, Sproull M, Beecken WD, Folkman J, et al. Radiation abscopal antitumor effect is mediated through p53. Cancer Res. 2003;63(8):1990-3
Wouters BG. Cell death after irradiation: how, when and why cells die. In: Joiner M, Van der Kogel AJ, eds. Basic Clinical Radiobiology. 4th ed. Hodder Arnold; 2009. p.27-40.
Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972;26(4):239-57.
Danial NN, Korsmeyer SJ. Cell death: critical control points. Cell. 2004;116(2):205-19.
Wong RS. Apoptosis in cancer: from pathogenesis to treatment. J Exp Clin Cancer Res. 2011;30: 87.
Levine B, Sinha S, Kroemer G. Bcl-2 family members: dual regulators of apoptosis and autophagy. Autophagy. 2008;4(5):600-6.
Campisi J, d’Adda di Fagagna F. Cellular senescence: when bad things happen to good cells. Nat Rev Mol Cell Biol. 2007; 8(9):729-40.
Lea DE. Actions of Radiation on Living Cells. Cambridge: Cambridge University Press; 1946.
Hutchinson F. Molecular basis for action of ionizing radiations. Science. 1961;134:533–538.
Zimmer KG. That was the radiobiology that was: a selected bibliography and some comments. In: Lett JT, Adler H, eds. Advances in Radiation Biology. Vol. 9. New York: Academic Press, Inc. 1981:411–467.
Kellerer AM, Rossi HH. The theory of dual radiation action. Curr Top Radiat Res. 1972;8: 85–158.
Alper T. Keynote address: survival curve models. In: Meyn RE, Withers HR, eds. Radiation Biology in Cancer Research. New York: Raven Press; 1980:3–18.
Davies, M.A. and Samuels Y. Analysis of the genome to personalize therapy for melanoma. Oncogene. 2010;29:5545–5555.
Jiang, BH and Liu LZ. PI3K/PTEN signaling in angiogenesis and tumorigenesis. Adv. Cancer Res. 2009; 102: 19–65.
Yuan, TLand Cantley LC. PI3K pathway alterations in cancer: variations on a theme. Oncogene. 2008;27:5497–5510.
Kazerounian, S, Yee KO, and Lawler J. Thrombospondins in cancer. Cell. Mol. Life Sci. 2008;65:700–712.
Beriswyl V and Christofori G. The angiogenic switch in carcinogenesis. Semin. Cancer Biol. 2009;19: 329–337.
Bergers G and Benjamin LE. Tumorigenesis and the angiogenic switch. Nat Rev Cancer. 2003;3: 401–410.
Berx G and van Roy F. Involvement of members of the cadherin superfamily in cancer. Cold Spring Harb Perspect Biol. 2009;1:a003129.
Cavallaro U, Christofori G. Cell adhesion and signalling by cadherins and Ig-CAMs in cancer. Nature Reviews Cancer. 2004;4(2):118-32.
Kessenbrock K, Plaks V, Werb Z. Matrix metalloproteinases: regulators of the tumor microenvironment. Cell. 2010;141(1):52-67.
Joyce JA and Pollard JW. Microenvironmental regulation of metastasis. Nat Rev Cancer 2009; 9: 239–252.
Palermo C, and Joyce JA. Cysteine cathepsin proteases as pharmacological targets in cancer. Trends Pharmacol. Sci. 2008; 29:22–28.
Mohamed, M.M., and Sloane, B.F. (2006). Cysteine cathepsins: multifunctional enzymes in cancer. Nat. Rev. Cancer 6, 764–775.
Qian BZ, Pollard JW. Macrophage diversity enhances tumor progression and metastasis. Cell. 2010;141(1):39-51.
Fares J, Y. Fares M, Khacfe H et al. Molecular principles of metastasis: a hallmark of cancer revisited. Signal Transduction and Targeted Therapy. 2020; 12(5):1-7.
Gourabi H, Mozdarani H. A cytokinesis-blocked micronucleus study of the radioadaptive response of lymphocytes of individuals occupationally exposed to chronic doses of radiation. Mutagenesis. 1998;13: 475–80.
Kumar D, Kumari S, Salian SR, Uppangala S, Kalthur G, Challapalli S, et al Genetic instability in lymphocytes is associated with blood plasma antioxidant levels in health care workers occupationally exposed to ionizing radiation. Int J Toxicol. 2016;35:327–35.
Abegglen LM, Caulin AF, Chan A, Lee K, Robinson R, Campbell MS, et al Potential mechanisms for cancer resistance in elephants and comparative cellular response to DNA damage in humans. JAMA. 2015;314:1850–60.
Vaupel P, Mayer A. Hypoxia in cancer: significance and impact on clinical outcome. Cancer Metastasis Rev. 2007;26(2):225-39.
Kumar P. Tumor hypoxia and anemia: impact on the efficacy of radiation therapy. Semin Hematol. 2000;37(4 Suppl 6):4-8.
Vaupel P. Tumor microenvironmental physiology and its implications for radiation oncology. Semin Radiat Oncol. 2004;14(3):198-206.
Melillo G. Targeting hypoxia cell signaling for cancer therapy. Cancer Metastasis Rev. 2007; 26(2):341-52.
Denko NC. Hypoxia, HIF1 and glucose metabolism in the solid tumor. Nat Rev Cancer. 2008;8(9):705-13.
Dewhirst MW, Cao Y, Moeller B. Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response. Nat Rev Cancer. 2008;8(6):425-37.
Lee K, Zhang H, Qian DZ, Rey S, Liu JO, Semenza L. Acriflavine inhibits HIF-1 dimerization, tumor growth, and vascularization. Proc Natl Acad Sci USA. 106(42): 17910-915.
Zundel W, Schindler C, Haas-Kogan D. Loss of PTEN facilitates HIF-1 mediated gene expression. Genes Dev. 2000;14(4):391-6.
Wysocki PJ. mTOR in renal cell cancer: modulator of tumor biology and therapeutic target. Expert Rev Mol Diagn. 2009;9(3):231- 41.
Pigott K, Dische S, Saunders MI. Where exactly does failure occur after radiation in head and neck cancer? Radiother Oncol. 1995;37 (1):17-9.
Shukovsky LJ. Dose, time, volume relationships in squamous cell carcinoma of the supraglottic larynx. Am J Roentgenol Radium Ther Nucl Med. 1970;108(1):27-9.
Little MP. Cancer after exposure to radiation in the course of treatment for benign and malignant disease. Lancet Oncol. 2001;2 (4):212- 20.
Rakıcı SY. Kanser Tedavisinde İmmunoterapi ve Radyoterapi. Rize Tıp Dergisi. 2021;1 (1):16-27.
Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972;26(4):239-57.
Wyllie AH. Apoptosis (the 1992 Frank Rose Memorial Lecture). Br J Cance.r 1993;67(2): 205-8.
Wyllie AH. The biology of cell death in tumours. Anti Cancer Res. 1985;5(1):131-6.
Slee EA, Harte MT, Kluck RM, Wolf BB, Casiano CA, Newmeyer DD, et al. Ordering the cytochrome c-initiated caspase cascade: hierarchical activation of caspases-2, -3, -6, - 7, -8, and -10 in a caspase-9-dependent manner. J Cell Biol.1999;144(2):281-92.
Adrain C, Martin SJ. The mitochondrial apoptosome: a killer unleashed by the cytochrome seas. Trends Biochem Sci 2001; 26(6):390-7.
