Chernobyl Disaster Effects PDF

Chernobyl disaster  Quiz Test your knowledge from last lecture! (Familial Hypercholesterolemia) https://kahoot.it Also available on:  Learning Outcomes Explain the...

Chernobyl disaster  Quiz Test your knowledge from last lecture! (Familial Hypercholesterolemia) https://kahoot.it Also available on:  Learning Outcomes Explain the effect of radiation on DNA. Describe the somatic health effects of Chernobyl radiation, 30 years on. Outline the transgenerational effects of Chernobyl radiation. Where is Chernobyl? Situated in the Ivankiv Raion of northern Kyiv Oblast, Ukraine. Close to the Ukraine - Belarus boarder. Chernobyl is about 90 kilometres north of Kyiv. Chernobyl Pripyat Chernobyl and Pripyat are cities in the Chernobyl Exclusion Zone.  Chernobyl Nuclear Power Plant Opened in 1977, under Soviet Union communist regime. * * * * Chernobyl nuclear power 1986 - 4 RBMK nuclear reactors. plant 10% of Ukraine's electricity at its full production. Reactor number 4 contained: ❖ 1,600 radioactive uranium-235 fuel rods ❖ 211 boron control rods Chernobyl Nuclear Power Plant Nuclear Fission Chain Reaction Control rods are neutron absorbing used to prevent reaction running away. 1:23am 26th April 1986 Safety testing of reactor 4 - ability to keep reactor cool in the event of power failure. Safety protocols were violated, and power surged inside the plant. A chain reaction of explosions occur inside the reactor. Explosions blew lid off reactor exposing core. Release of radioactive material into the atmosphere. Worlds largest nuclear disaster!  Worlds largest nuclear disaster A cloud of radioactive smoke and dust drifted over Europe carried by the wind. Fire burnt for 10 days. Classified “Level 7” (highest level) on the International Nuclear and Radiological Event Scale Fukushima Daiichi nuclear disaster, the only other “Level 7” event. Major radioactive substances Up to 30% of Chernobyl’s 190 metric tons of uranium- 235 and fission products were now in the atmosphere. 1996 d = Days; a = Years  Exclusion zone response After 36 hours a 10km (6.2mile) area evacuated of 49,000 people primarily from Pripyat. Later increased to 30km (19mile) with an additional 68,000 people evacuated. Present day Exclusion Zone - irregular shaped spanning 4,000 sq km (1,600 sq mile). Reactor 4 is encased in a giant metal concrete sarcophagus to halt the release of radiation into the atmosphere. Present Day Chernobyl Photos from Dr Aidan Seeley Chernobyl radiation dose A dosimeter measures the external dose of radiation from the environment. The readings are in units called microsieverts (µSv). Global average annual dose of 2400 µSv from natural background radiation. Population category Number Average dose (µSv) Plant workers and Firefighters 600 (134) 700,000 - 13,400,000 Liquidators 530,000 120,000 Evacuees from Exclusion zone 115,000 30,000 Residents of contaminated countries - 9,000 Residents of other European countries - 1,000 Chernobyl radiation sources  Effects of Radiation The effects of radiation on cells dependent on: The dosage of the radiation received. The location of the cell regarding tissue. Whether the cell is a somatic or germ line cell. How does radiation effect the cell: Could pass through the cell without damaging the DNA. Could damage the DNA directly. Could indirectly damage the DNA through free radicals. Direct radiation DNA damage 1. Changing the chemical structure of the bases. 2. Breaking the sugar-phosphate backbone. (Single stranded or double stranded). 3. Breaking the hydrogen bonds connecting the base pairs. Indirect radiation DNA damage Radiation can disrupt water molecules. Hydrogen (H+) and Hydroxyl (OH-) ions = Free radicals Ions can react with hydrogen atoms in the DNA resulting in damage.  Effects of Radiation on DNA DNA Damage DNA Repair Direct Base Excision Normal Cell Survival Base modifications Repair (BER) Successful Functioning Single stranded repair breaks Unsuccessful repair Non repairable damage Mutations Chromosomal aberrations Free Interstrand Homologous Radicals recombination Cell Death Cell Survival Indirect cross links OH-, H+ (S and G2 phase) Double stranded breaks Non- homologous H2O end joining (NHEJ) Senescence Malignant (all cell cycle stages) Transformation Apoptosis Necrosis Premature differentiation  Chernobyl Genome Damage Increased genome damage including chromosome aberrations and micronuclei. Particularly increased frequency of dicentric chromosomes. Germline minisatellite mutation rate doubling in frequency after the Chernobyl accident among offspring of irradiated parents. Minisatellite Fucic. A., et al. (2016). Follow-up studies on genome damage in children after Chernobyl nuclear power plant accident. Arch Toxicol, 90:2147–2159 Dubrova. Y.E., et al. (1996). Human minisatellite mutation rate after the Chernobyl accident. Nature.  Transgenerational effects Aim: Does radiation exposure results in genetic changes that can be passed from parent to offspring? Method: Analysed the complete genomes of 130 people born between 1987 and 2002 and their 105 mother-father pairs. One or both of the parents had been workers who helped clean up from the accident or had been evacuated because they lived in close proximity to the accident site. Each parent was evaluated for protracted exposure to ionizing radiation. Result: No evidence of an increase in the number or types of de novo mutations in their children born between 46 weeks and 15 years after the accident. Yeager M, et al. (2021). Lack of transgenerational effects of ionizing radiation exposure from the Chernobyl accident. Science. Somatic health effects of Chernobyl: 30 years on Cardiovascular disease Haematological malignancies Thyroid cancer Iodine - Thyroid Iodine becomes localized in the thyroid gland. Iodine essential for thyroid hormones synthesis - triiodothyronine (T3) and tetraiodothyronine (T4). Exposure to Iodine-131 Risk factors: ❖ Young age- consuming large quantities of milk and smaller thyroid glands. ❖ Radiation dose ❖ Iodine deficiency Treatment: saturating the thyroid with regular, stable iodine-127. Iodine-131 - Thyroid Cancer 4,000 thyroid cancer cases diagnosed between 1992 and 2002 in individuals who were children or adolescents at the time of the accident in Ukraine, Belarus and Russia. Ricarte-Filho, et al., (2013). Identification of kinase fusion oncogenes in post-Chernobyl radiation-induced thyroid cancers. J Clin Invest. Morton. L et al., (2021). Radiation-related genomic profile of papillary thyroid cancer after the Chernobyl accident. Science Iodine-131 - Thyroid Cancer Mutations Somatic driver mutations primarily intrachromosomal gene fusions/rearrangements Hallmarks of non-homologous end- joining repair. Gene mitogen-activated protein kinase pathway (MAPK or MAP kinase). MAPKs regulate proliferation, gene expression, differentiation, mitosis, cell survival, and apoptosis. Ricarte-Filho, et al., (2013). Identification of kinase fusion oncogenes in post-Chernobyl radiation-induced thyroid cancers. J Clin Invest. Iodine-131 - Thyroid Cancer Mutations Ricarte-Filho, et al., (2013). Identification of kinase fusion oncogenes in post-Chernobyl radiation-induced thyroid cancers. J Clin Invest. Haematological malignancies Various types of oncohematological diseases developing 10–20 years after Chernobyl accident were registered in a group of clean-up workers under study. Percentage of Myelodysplastic syndromes among clean-up workers tended to exceed the general population examined at the same period. Still a point of controversy. Gluzman. D., et al. (2006) Patterns of hematological malignancies in Chernobyl clean-up workers (1996-2005). Experimental Oncology. 28(1):60-3.  Circulatory disease Objective: To estimate the circulatory system disease death rates for people living in areas contaminated after the Chornobyl accident. Post-accident period (1988-2010). Methods: Residents of contaminated areas were grouped according to cumulative dose values: Cohort 1 = 5.6-20.99 mSv Cohort 2 = 21.00-50.99 mSv Results Significantly higher cardiovascular mortality among members of the cohort 2 vs. cohort 1. Buzunov. V.O, et al., (2013) Radiation dose- and sex-dependent cardiovascular mortality in residents of contaminated areas after the Chornobyl NPP accident, 1988-2010 observation period. Probl Radiac Med Radiobiol, (18):50-8.  Neural Tube Defects During 2011–2016 period, recorded Cesium-137 whole body counts from 11,784 pregnant women residing across Rivne Province. The daily dietary consumptions of Cesium-137 often exceed the recommended upper limits by the state. During the 2000–2015 period there were 247,158 live births, 449 instances of neural tube defects, and 43 instances of Microcephaly. For comparison of congenital anomalies rates in Europe, data was extracted from EUROCAT reports. Neural tube defects in Rivne are the highest, followed by those reported in Wales and Northern England. Neural Tube Defects (NTD) prevalence rates during the 2000–2015 period in Europe. Werteleckia, W, et al. (2018) Chornobyl, radiation, neural tube defects, and microcephaly. European journal of medical genetics. Red Forest of the Exclusion Zone Now Thank you for listening to todays lecture… if it’s a topic that interests you, please do some around reading to broaden your understanding of the topic there is lots of interactive videos as well as scientific articles available through ‘pubmed’ search engine. Chernobyl Disaster Effects: Revisiting the Nuclear Accident Site 20 Years Later - YouTube https://www.youtube.com/watch?v=ldYeFLZq h3Q Epigenetic radiation damage DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. DNA methylation in the gene promotor typically acts to repress gene transcription. Global Hypomethylation and Site specific Hypermethylation Belli and Tabocchini 2020