ISSN 00063509, Biophysics, 2011, Vol. 56, No. 3, pp. 577–583. © Pleiades Publishing, Inc., 2011. Original Russian Text © I.I. Pelevina, G.G. Afanas’ev, A.V. Aleshchenko, M.M. Antoshchina,V.Ya. Gotlib, A.A. Konradov, O.V. Kudryashova, E.Yu. Lizunova, A.N. Osipov, N.I. Ryabchenko, A.M. Serebryanyi, 2011, published in Radiatsionnaya Biologiya. Radioekologiya, 2011, Vol. 51, No. 1, pp. 154–161. RADIOBIOLOGY AND RADIOECOLOGY The Molecular and Cellular Consequences of the Chernobyl Accident I. I. Pelevinaa, G. G. Afanas’eva,†, A. V. Aleshchenkob, M. M. Antoshchinac, V. Ya. Gotliba, A. A. Konradovb,†, O. V. Kudryashovaa, E. Yu. Lizunovaa, A. N. Osipova, N. I. Ryabchenkoc, and A. M. Serebryanyib a Institute of Chemical Physics, Russian Academy of Sciences, Moscow, 119991 Russia b Institute of Biochemical Physics, Russian Academy of Sciences, Moscow, 119334 Russia c Medical Radiological Research Center, Russian Academy of Medical Sciences, Obninsk, 249036 Russia Email: [email protected] Received July 5, 2010 Abstract—In this paper the results of research at 5–10 and 24 years after the Chernobyl accident are summa rized. These results include the investigation of genomic instability, formation of the adaptive response, genome damage, and oxidative status. The studies were performed on cells in culture, mice, children and adults who lived in the contaminated areas, and liquidators of the consequences of the Chernobyl accident. Inhibition of cell proliferative activity, late cell death, and the increase in micronucleus and giant cell fre quency were observed after the exposure of cells in culture in the accident zone followed by their culturing in laboratory conditions. In the progeny of the exposed cells, the effect of enhanced radiosensitivity was detected. Thus, it can be assumed that exposure of parental cells in culture in the area of the accident induced genomic instability that resulted in the development of various abnormalities in progeny cells. At the organ ism level, the Chernobyl zone exposure of mice caused an increase in radiosensitivity; as well, a decrease in the endotheliocyte density in the cerebral cortex and other brain tissues was observed. In the blood lympho cytes of children stimulated by PHA, a more than two times increase in micronucleus cell frequency was detected. A reduced number of individuals with significant adaptive response was found in both the juvenile and adult groups. In all investigated populations, an increased number of individuals with enhanced radi osensitivity were observed in response to lowdose radiation exposure. At 24 years after the accident liquida tors were subjected to examinations, which revealed an increased frequency of cells with micronuclei and chromosometype aberrations in blood lymphocytes, an elevated level of DNA double strand breaks, and a reduced level of reactive oxygen species compared to those of the control group. This means that the genomic instability that was accumulated by the residents of the contaminated regions and liquidators as a result of the accident leads to damage of the genetic apparatus, an increase in radiosensitivity, and hypoxia as late conse quences that all are risk factors and increase the probability of the development of tumor and nontumor dis eases. The development of the abovementioned pathological processes may occur in the distant future. Keywords: blood lymphocyte, liquidators of the Chernobyl accident consequences, genome instability, cell death, genome damage, reactive oxygen species, late consequences DOI: 10.1134/S0006350911030237 The Chernobyl accident opened a new era of radio The effects of low dose radiation differ from that of biology where much attention has been given to stud high dose exposure. According to the classical model ies of the effects of low dose radiation. Experimental of radiation effects, the response of discrete cell targets is very individual and depends on the number of non research on isolated cells, animals, and lymphocytes repaired and incorrectly DNA lesions. In the modern of individuals who were exposed to irradiation, such as concept, response processes may occur at a distance liquidators or the residents of the contaminated zones, that is greater than the cell size; these responses are played an important role in achieving a better under controlled by cellsignaling pathways and a direct hit is standing of postaccident effects. These studies enable not a compulsory for cell damage. As a result of this one to gain knowledge of the early and late conse concept change a new approach to the understanding quences of low dose radiation exposure and possible and assessment of the effects of radiation has arisen. mechanisms of their development that allows solving According to this approach, epigenetic abnormalities the problem of the formation and development of the may be the most important event, as it leads to the consequences of the Chernobyl accident. conversion of normal cells into malignant ones with out direct mutations. In nonexposed cells, changes in † Deceased. the gene expression, DNA repair, chromosome aber 577 578 PELEVINA et al. Table 1. Cell survival (clonogenic ability) in the progeny of main phenomena that lead to a number of various cells exposed in the 10kilometer zone around the Cherno consequences [11]. byl Nuclear Power Plant (0.096 Gy total irradiation dose) In this work, the results of many years of research Number In the Chernobyl (at 5–10 years and 24 years after the Chernobyl acci of generations after Control accident zone dent) are summarized. These are data on the cellular initial exposure and cytogenetic manifestations of genomic instability, 6 0.21 0.14* and the formation of the adaptive response, as well as genome damage (the micronucleus test, metaphase 12 0.17 0.06* analysis of chromosome aberrations, and comet assay 18 0.31 0.25 analysis of the number of DNA breaks). All tests were 21 0.36 0.15* carried out either in areas that were contaminated as a 24 0.36 0.15* result of the Chernobyl accident, such as the Cherno byl Nuclear Power Plant near the nuclear reactor, on * The statistically significant difference between the con χ2 the border with the “Red Forest,” or in the Bryansk trol and irradiated populations of cells ( criterion). region (Klintsy, Vyshkov, and Novozybkov areas) or by using biological samples from liquidators of the Cher nobyl accident [12, 13]. The studies were performed Table 2. The number of giant cells (per 1000 cells analyzed) in the progeny of cells exposed in the 10kilometer zone using mammalian and human cells in culture, the around the Chernobyl Nuclear Power Plant blood lymphocytes of children and adults, and, at the organism level, those of small laboratory animals that Number Time of exposure – total dose were exposed to the environmental conditions of the of generations Control industrial disaster. after initial 1 days – 0.024 Gy 6 days – 0.144 Gy exposure In cells of a tissue culture that were exposed to irra diation in the accident area for 1, 4, or 6 days, then 46270– cultivated under normal laboratory conditions for 650136*– many cellcycle passages, and then subjected to anal 96280– yses of the consequences of genomic instability, inhi bition of cell proliferative activity in a period of six to 14 60 85 – seven generations after cell culture exposure in the 16 49 62 127* Chernobyl zone was observed, as the control level of 24 63 50 154* cell proliferation was achieved only by the eighth gen eration (control cultures were maintained under simi * The statistically significant difference between the control and irradiated populations of cells (χ2 criterion). lar ecological and other conditions in areas that were not contaminated with radionuclides). The number of cells in the control increased by approximately seven rations, mutations, cell death, and radiationinduced and a half times, whereas after the abovementioned genome instability occur. The genes that regulate radi exposure the value of the growth factor was two times osensitivity are widely studied in epidemiological smaller. It may be assumed that such inhibition of the proliferative activity in the progeny of the exposed research and risk management as markers of the genetic cells is caused by the induction of genomic instability sensitivity of individuals and populations [1, 2]. and, consequently, an elevated level of cell death in the In the last 15 years, the nontargeted effects of low parental culture. This assumption is supported by the dose radiation, such as genomic instability (GI), the fact that the clonogenic ability of cells exposed in the adaptive response (AR), the bystander effect, horme 10kilometer zone around the Chernobyl Nuclear sis, and, at the organism level, the clastogenic effect, Power Plant is lower than that of nontreated cells in have been described [3–10]. the period of 24 generations (Table 1). A very similar situation was observed when the number of giant cells It can be assumed that the problem of the late con was studied as their number increased by more than sequences of the Chernobyl accident is mainly about a two times in the exposed population and does not deep understanding of the effects and mechanisms of decreased in the period of 16–24 generations the actions caused by low dose radiation. It is (Table 2). extremely important that in response to low dose radi Radiosensetivity increase is another important ation GI is induced, which may promote other conse phenomenon that can be classified as a manifestation quences in response to external effects, stress, and of genomic instability; it is detected in the progeny of irradiation in the case of additional load. Therefore, cells exposed in the accident zone. Additional irradia one might suppose that GI induced by low dose radia tion treatment at a 3 Gy dose affects cell survival or the tion in cells of liquidators and residents of the contam clonogenic ability of the progeny of the exposed cells, inated areas of the Chernobyl accident is one of the which becomes significantly lower than that of the BIOPHYSICS Vol.