m-FISH analysis reveals complexity of chromosome aberrations in individuals occupationally exposed with internal plutonium: A pilot study to assess the relevance of complex aberrations as biomarkers of exposure to high-LET α particles

We recently demonstrated that a significant proportion of apparently stable insertions induced after exposure to a mean of 1 α particle/cell, detected using 3-colour FISH, were part of larger unstable complexes when visualised by 24-colour FISH. Interestingly, regardless of the long-term persistence capability of the cell, the complexity of each α particle-induced complex appeared to be specific to the nuclear traversal of a single -particle. To assess whether aberrations of a similar complexity are observed in vivo and also to examine the usefulness of detecting such aberrations as a biomarker of chronic exposure to α particles, we have carried out a limited pilot study of Russian workers with large body burdens of -particle emitting plutonium (Pu). We found unstable cells containing non-transmissible complex aberrations in all of the Pu exposed subjects analysed by m-FISH. In addition, all of the complexes seen were consistent with those previously observed in vitro. Non-transmissible complex aberrations were more common than transmissible-type complexes, consistent with on-going/chronic exposure and insertions were dominant features of both type of complex. Accordingly, this preliminary study supports the proposal that aberration complexity and non-transmissibility are the major cytogenetic features of α particle exposure that could potentially be exploited as a specific indicator of chronic exposures to high-LET α particles

Флюоресцентная гибридизация in situ: практическое применение в онкоурологии

Tumor markers for diagnosis of bladder cancer and defining the prognosis of the disease have been actively studied for past decade. FISH-study demonstrates the highest sensitivity and specificity. Abbot Company has developed a diagnostic test system «UroVision» which includes colored DNA-probes referring to 3, 7, 17 and 9p21 chromosomes. This system use provides clinicians with insights into an early diagnosis, prognosis and monitoring of efficacy of anticancer therapy.

Клиническое применение FISH-метода в ранней диагностике поверхностного рака мочевого пузыря

Patients with primary diagnosis of bladder cancer (42 persons) were studied. FISH analysis performed in all patients showed the following results: 39 (93%) patients were FISH positive and 3 (7%) were FISH negative. The molecular cytogenetic criterion for determining the grade of differentiation of Ta and T1 tumors — chromosomal hyperploidy in morphologically abnormal cells, was suggested. All patients demonstrating increased amount (more than 26%) of abnormal cell with hyperploidy of chromosomes 3, 7 and 17 were found to have high grade malignancies.

Fluorescent in situ hybridization: clinical use in oncourology

Tumor markers for diagnosis of bladder cancer and defining the prognosis of the disease have been actively studied for past decade. FISH-study demonstrates the highest sensitivity and specificity. Abbot Company has developed a diagnostic test system «UroVision» which includes colored DNA-probes referring to 3, 7, 17 and 9p21 chromosomes. This system use provides clinicians with insights into an early diagnosis, prognosis and monitoring of efficacy of anticancer therapy

The Continuous Observation by Chromosome Aberration Elimination at Irradiated Persons

One from a problem of biological dosimetry is the dose evaluation in remote time after irradiation. This takes place in certain percent of cases of acute irradiation, for ex-ample, when patient entrance in hospital is delayed. The retrospective dose evaluation is necessary for confirmation of irradiation fact and determination of quantity of possible absorbed dose in aims of medical social examination and potential judicial trials which are associated with requirements of a compensation of damage caused by health. There-fore the investigation of chromosome aberration rate dynamics of patients injured in a result of Chernobyl accident is very important. In this situation the fact of presence of primary cytogenetic analysis results of peripheral blood lymphocyte cultures established in nearest days and weeks after irradiation for many number of injured patients is espe-cially essential. It allows to make the comparison between primary and repeated investi-gations. Chernobyl patients (73 humans investigated in during 12 years after irradiation) were divided by three groups depending on primarily evaluated dose by medium dicen-tric frequency: patients irradiated by 0,2-2,4 Gy (30 individuals, 90 cultures); patients ir-radiated by 2,6-4,4 Gy (28 individuals, 117 cultures) and patients irradiated by 4,6-9,8 Gy (15 individuals, 64 cultures). The cytogenetic analysis was produced by FPG-method. Also the cytogenetic data of nearest time after irradiation testified to relatively uniform irradiation of basic body mass for almost all injured patients. We used double exponential model how in the article IAEA (1998) for Goiania pa-tients for the mathematical description of elimination of dicentrics and unstable chromo-some aberrations. A speed of decrease of frequency of dicentrics in cells with dicentrics in middle was more than for frequencies of dicentrics and unstable aberrations by 100 analyzed cells. In all cases the elimination speeds of cytogenetic indexes of unstable aberrations was the more the more primary absorbed dose. High individual variability of this process was observed. Qdr index which is often proposed for retrospective dose indication sub-mitted these principles also. The middle speed of its decrease was less than for frequen-cies of dicentrics and unstable aberrations by 100 analyzed cells but more than for fre-quency of dicentrics in cells with dicentrics. As against dicentrics and other unstable ab-errations atypical chromosomes frequency in whole was approximately constant in dur-ing 12 years of observation in spite of high individual variability. However in late period atypical chromosomes were contained mainly in stable cells but not unstable cells

Genomic damage in children accidentally exposed to ionizing radiation: a review of the literature

During the last decade, our knowledge of the mechanisms by which children respond to exposures to physical and chemical agents present in the environment, has significantly increased. Results of recent projects and programmes focused on children's health underline a specific vulnerability of children to environmental genotoxicants. Environmental research on children predominantly investigates the health effects of air pollution while effects from radiation exposure deserve more attention. The main sources of knowledge on genome damage of children exposed to radiation are studies performed after the Chernobyl nuclear plant accident in 1986. The present review presents and discusses data collected from papers analyzing genome damage in children environmentally exposed to ionizing radiation. Overall, the evidence from the studies conducted following the Chernobyl accident, nuclear tests, environmental radiation pollution and indoor accidental contamination reveals consistently increased chromosome aberration and micronuclei frequency in exposed than in referent children. Future research in this area should be focused on studies providing information on: (a) effects on children caused by low doses of radiation; (b) effects on children from combined exposure to low doses of radiation and chemical agents from food, water and air; and (c) specific effects from exposure during early childhood (radioisotopes from water, radon in homes). Special consideration should also be given to a possible impact of a radiochemical environment to the development of an adaptive response for genomic damage. Interactive databases should be developed to provide integration of cytogenetic data, childhood cancer registry data and information on environmental contamination. The overall aim is to introduce timely and efficient preventive measures, by means of a better knowledge of the early and delayed health effects in children resulting from radiation exposure