Radiobiology (HTI 27103) Tissue Effects of Radiation Damage Department of Health Technology and Informatics Liang-Ting Lin Outline – Tissue Effects of Radiation Damage • Both molecular and DNA damage are invisible and feelingless • Genetic profile – Genotype • Somatic expression – Phenotype • The consequence of radiation damage shows up in a physiological and visible scale Effects of radiation – Hair removal • Albert Geyser invented Cornell tube that claims the elimination of safety issue by lead shielding. • Geyser founded a company, Tricho System, for hair removal treatment in 1924. • Hair removal with painless, fast, and permanent attracted lots of women during the time. An advertisement of Tricho System in 1926 3 Effects of radiation – Radium everywhere https://io9.gizmodo.com/seriously-scary-radioactive-consumer-products-from-the-498044380 Effects of radiation – Radium water https://orau.org/health-physics-museum/collection/radioactive-quack-cures/jars/curie-re-generator-jar-1925-1930.html Effects of radiation – Radium water • William J.A. Bailey patented RADITHOR to stimulate endocrine and cure asthma, pain, and constipation. - 1918 • Eben Byers consistently took this medication from 1927-1930, while he found his health was greatly improved. By the time, he had taken 1,400 bottles. Died (1932) due to radium poisoning. The Wall Street Journal http://theconversation.com/when-energy-drinks-actually-contained-radioactive-energy-67976 Effects of radiation – Radiation Hormesis Effects of radiation – Genetic or Somatic? Overview – The story in a glance Dominant Genetic Effects inherited Recessive Stochastic Effects Radiation-induced Effects in Human Beings individual Late Effects Somatic Effects Deterministic Effects Early Effects Somatic effect – Syndromes • Somatic damage: effects that expressed during the individual’s life-span • Cataractogenesis, pneumonitis, and skin reactions. Somatic effect – Time of onset of skin reactions Early effects (within weeks) Late effects (up to years) Cataract? Cancers? Resource: Hiroshima and Nagasaki A-bomb victims 12 Early / Acute Effect • Occur soon after radiation exposure • Within weeks Dry desquamation Skin reaction Moist desquamation Early / Acute Effect Nausea & vomiting Oral mucositis Late Effect of Radiation Telangiectasia Pigmentation Genetic or Somatic effect – infertility Overview – The story in a glance Dominant Genetic Effects inherited Recessive Stochastic Effects Radiation-induced Effects in Human Beings individual Late Effects Somatic Effects Deterministic Effects Early Effects Genetic effect – hereditary of radiation 1. It is a commonly held view that radiation produces bizarre mutants and monsters. 2. Radiation does not result hereditary effects that are new or unique but rather increases the frequencies of the same mutations that already occur spontaneously or naturally in that species. 3. Really?? Genetic effect – hereditary of radiation Jonathan Russell concerns about the radiotherapy that he received during childhood would affect his 3-year-old daughter News release (Oct 2009): http://www.eurekalert.org/multimedia/pub/17296.php?from=146213 Chernobyl – the aftermath Hereditary effects – examples Hereditary effects – Mega Mouse Project Hereditary effects – Mega Mouse Project • W.L. Russell and L.B. Russell began a large-scale animal study by irradiating mice with different dose rate since 1940s. • They observed the phenotypic changes • Coat colors, eye colors • Approx. 7 million mice were studied Hereditary effects – Mega Mouse Project 1. Correlate to DNA contents and size of nucleus - mutation happens by chance 2. The radiosensitivity of different mutations varies by a factor of 35 – only average mutation rate can be presented - mutations are randomly distributed, but some particular sites are more sensitive 3. The male mouse is more sensitive to radiation than that of female - the meiosis is still working on 4. The genetic consequences of a given dose can be greatly reduced if a time interval is allowed between irradiation and conception - DNA damage repair takes place - The reason of fractionation The Selby-Russel Dispute Overview – The story in a glance Dominant Genetic Effects Recessive Stochastic Effects Radiation-induced Effects in Human Beings Late Effects Somatic Effects Deterministic Effects Early Effects Stochastic effects • Cellular effect • Has NO threshold • Inheritable • Occurs in low dose and increases in frequency with increasing dose • Examples: • Mutation (affected by dose rate & fractionation) • Carcinogenesis (complex event, other factors involved e.g., cell aging, carcinogens etc.) Stochastic effects Undefined region Stochastic effects - radioprotection • Radiation Protection: • Threshold value (ICRP) for organs are not applicable • Follow ALARA principle • Relevant to diagnostic radiography • The main concern in radiation protection. https://www.irsn.fr/FR/connaissances/Sante/exposition-travailleurs-santeradioprotection/radioprotection-travailleurs/bilan-annuel-exposition-travailleurs-France/Pages/0Exposition-travailleurs-France-Sommaire.aspx#.XF-d688zab8 Deterministic effects • Also called non-stochastic effect • Organ/tissue effect • Presence of the threshold • Individual event • Effects do NOT appear below a certain dose • Effects increases with doses after threshold • Effects depends on dose rate and fractionation • Example: cataract, skin reaction, fibrosis Deterministic effects – radioprotection • Threshold value (ICRP) for organs are applicable • ALARA principle NOT applicable • Relevant to radiotherapy • Different organs have different dose limits • Therapeutic ratio must be observed to prevent normal tissue necrosis https://www.itnonline.com/content/aapm-studies-reinforce-clinical-value-elekta-monaco-treatment-planning-system Deterministic effects – RT planning Stochastic effect vs. Deterministic effect • Single cell effect • Expression of cell transformation • No threshold • Mainly low dose effect • Relevant to protection in diagnostic radiology • Genetic transformations, carcinogenesis • Organ/Tissue effect • Expression cell killing • Threshold present • High dose level effect • Relevant to normal tissue protection in radiotherapy • Early & late tissue reactions Stochastic effect vs. Deterministic effect Shigematsu, N., Fukada, J., Ohashi, T., Kawaguchi, O., & Kawata, T. (2012). Nuclear disaster after the Earthquake and Tsunami of March 11. Keio Journal of Medicine, 61(1), 28-34. https://doi.org/10.2302/kjm.61.28 Crosstalk between Genetic and Somatic Effects https://www.env.go.jp/en/chemi/rhm/basic-info/1st/03-01-01.html
