Análisis citogenético en linfocitos de trabajadores expuestos a radiación ionizante en una unidad de cardiología intervencional de Chile: estudio piloto y revisión de la literatura / Citogenetic effects upon lymphocyes in subjects exposed to ionizing radiadion in an interventional laboratory cardiology: pilot study and literature review

ANTECEDENTES: Un número creciente de artículos está llamando la atención en forma consistente sobre la eventual asociación que existe entre los denominados trabajadores ocupacionalmente expuestos a bajos niveles de radiación ionizante (POEs) y una mayor frecuencia de aberraciones cromosómicas, a nivel Sudamericano estos estudios son escasos. OBJETIVO: Evaluar la frecuencia de aberraciones cromosómicas en linfocitos de sangre periférica de POEs de un hospital y de sujetos sanos. Adicionalmente, se realizó una revisión exhaustiva de los artículos que a la fecha abordaron este tema. MATERIAL Y MÉTODO: Se condujo un análisis citogenético destinado a cuantificar las aberraciones cromosómicas en sangre periférica de linfocitos de 6 POEs de la unidad de Cardiología Intervencional y, como controles, 6 muestras de sujetos de la población general fueron analizadas. RESULTADOS: Se observó un importante contraste en el número de aberraciones cromosómicas presentadas en los POEs versus la población general no expuesta a radiaciones ionizantes, siendo esta de una relación de 6:1, respectivamente. CONCLUSIÓN: Los resultados preliminares indican una mayor frecuencia de aberraciones cromosómicas en los POEs versus la población general, sin embargo, se deberá esperar los resultados de la segunda fase de investigación, donde al ampliar la muestra en análisis se podrán obtener conclusiones estadísticamente significativas.

BACKGROUND: There is growing evidence of an increased number of chromosomes aberrations in subjects exposed to low levels of ionizing radiation (POEs). There are few studies on this subject in Latin America AIM: To evaluate the frequency of chromosome aberrations in lymphocytes obtained from peripheral blood in subjects working in laboratories where low levels of ionizing radiation are present and to compare these findings to those of unexposed subjects. METHODS: A cytogenic analysis to quantify chromosome aberrations was performed in 6 POs subjects from a cardiology invasive laboratory and 6 controls from a general unexposed population. RESULTS: Compared to controls, an approximately 6-fold increase in the number of chromosome aberrations was observed.in subjects exposed to ionizing radiation CONCLUSION: These preliminary results indicate that there is an increased number of chromosome aberrations in subjects exposed to low levels of ionizing radiation, as occurs in people working in a cardiology interventional laboratory. Studies in large numbers of subjects and preferably followed prospectively are needed to evaluate more precisely this effect.

A dose-response curve for biodosimetry from a 6 MV electron linear accelerator

Biological dosimetry (biodosimetry) is based on the investigation of radiation-induced biological effects (biomarkers), mainly dicentric chromosomes, in order to correlate them with radiation dose. To interpret the dicentric score in terms of absorbed dose, a calibration curve is needed. Each curve should be constructed with respect to basic physical parameters, such as the type of ionizing radiation characterized by low or high linear energy transfer (LET) and dose rate. This study was designed to obtain dose calibration curves by scoring of dicentric chromosomes in peripheral blood lymphocytes irradiated in vitro with a 6 MV electron linear accelerator (Mevatron M, Siemens, USA). Two software programs, CABAS (Chromosomal Aberration Calculation Software) and Dose Estimate, were used to generate the curve. The two software programs are discussed; the results obtained were compared with each other and with other published low LET radiation curves. Both software programs resulted in identical linear and quadratic terms for the curve presented here, which was in good agreement with published curves for similar radiation quality and dose rates.

Transient cytotoxicity of 131I beta radiation in hyperthyroid patients treated with radioactive iodine.

Background & objectives: Radioiodine (131I) or radioactive iodine in low doses is used worldwide as the first line of management in the treatment of hyperthyroidism. Information is available on the extent and severity of cell damage after a high dose radioiodine (131I) therapy for thyroid cancer, but information is scanty on its cellular effects, its extent and severity of cell damage after a low dose 131I therapy. The present investigation was aimed to study the cytotoxic effects of a low dose 131I therapy in varying doses as is normally being used in routine clinical practice in the treatment of various forms of hyperthyroidism. Methods: Peripheral blood lymphocytes were analyzed in 32 hyperthyroid patients. All of them received 131I in the form of sodium iodide solution orally. Blood lymphocytes were studied for the presence of chromosomal aberrations (CA) and micro nucleus (MN) using micronucleus assay. Blood samples of these patients were drawn prior to the treatment, on 7 thand 30 thdays after the treatment. Results: The results indicated a positive relationship between 131I dose, CA and MN frequency. A statistically significant increase in CA and MN frequency in day 7 post- therapy and a decrease in mean levels of CA and MN on day 30 post-therapy were observed when compared to pre-therapy. Interpretation & conclusions: This study showed that the cytogenetic damage induced by 131I in low doses i.e., less than 555MBq was minimal and reversible. Patients can be motivated to undertake this safe and easy procedure as a first line of therapy in the treatment of hyperthyroidism.

Induction of chromosomal aberrations in human primary fibroblasts and immortalized cancer cells exposed to extremely-low-frequency electromagnetic fields

Rapidly increasing possibilities of exposure to environmental extremely low-frequency electromagnetic fields [ELF-EMF] have become a topic of worldwide investigation. Epidemiological and laboratory studies suggest that exposure to ELF-EMF may increase cancer risk therefore assessment of chromosomal damage in various cell lines might be of predictive value for future risk estimation. Primary cultures of fibroblasts from human skin biopsy were exposed to continuous extremely low-frequency electromagnetic fields [3, 50 and 60 Hz, sinusoidal, 3h, and 4 mT]. Also immortalized cell lines, SW480, MCF-7 and 1321N1 were exposed to continuous ELF-EMF [50 Hz, sinusoidal, 3 h, 4 mT]. Metaphase plates were prepared according to standard methods and stained in 5% Giemsa solution. Chromosomal aberrations of both chromosome and chromatid types were scored to evaluate the effects of ELF-EMF on primary or established cell lines. Results indicate that by increasing the frequency of ELF-EMF, chromosomal aberrations were increased up to 7-fold above background levels in primary human fibroblast cells. In addition, continuous exposure to a 50 Hz electromagnetic field led to a significant increase in chromosomal aberrations in SW480, MCF-7 and 1321N1 cell lines compared to sham control. Results obtained indicate that ELF-EMF has the potential for induction of chromosomal aberrations in all cell types

Dose assessment by quantification of chromosome aberrations and micronuclei in peripheral blood lymphocytes from patients exposed to gamma radiation

Scoring of unstable chromosome aberrations (dicentrics, rings and fragments) and micronuclei in circulating lymphocytes are the most extensively studied biological means for estimating individual exposure to ionizing radiation (IR), which can be used as complementary methods to physical dosimetry or when the latter cannot be performed. In this work, the quantification of the frequencies of chromosome aberrations and micronuclei were carried out based on cytogenetic analyses of peripheral blood samples from 5 patients with cervical uterine cancer following radiotherapy in order to evaluate the absorbed dose as a result of partial-body exposure to 60Co source. Blood samples were collected from each patient in three phases of the treatment: before irradiation, 24 h after receiving 0.08 Gy and 1.8 Gy, respectively. The results presented in this report emphasize biological dosimetry, employing the quantification of chromosome aberrations and micronuclei in lymphocytes from peripheral blood, as an important methodology of dose assessment for either whole or partial-body exposure to IR.

Roles of nibrin and ATM/ATR kinases on the G2 checkpoint under endogenous or radio-induced DNA damage

Checkpoint response to DNA damage involves the activation of DNA repair and G2 lengthening subpathways. The roles of nibrin (NBS1) and the ATM/ATR kinases in the G2 DNA damage checkpoint, evoked by endogenous and radio-induced DNA damage, were analyzed in control, A-T and NBS lymphoblast cell lines. Short-term responses to G2 treatments were evaluated by recording changes in the yield of chromosomal aberrations in the ensuing mitosis, due to G2 checkpoint adaptation, and also in the duration of G2 itself. The role of ATM/ATR in the G2 checkpoint pathway repairing chromosomal aberrations was unveiled by caffeine inhibition of both kinases in G2. In the control cell lines, nibrin and ATM cooperated to provide optimum G2 repair for endogenous DNA damage. In the A-T cells, ATR kinase substituted successfully for ATM, even though no G2 lengthening occurred. X-ray irradiation (0.4 Gy) in G2 increased chromosomal aberrations and lengthened G2, in both mutant and control cells. However, the repair of radio-induced DNA damage took place only in the controls. It was associated with nibrin-ATM interaction, and ATR did not substitute for ATM. The absence of nibrin prevented the repair of both endogenous and radio-induced DNA damage in the NBS cells and partially affected the induction of G2 lengthening.

Effects of gamma-irradiation on the infectivity and chromosome aberration of Clonorchis sinensis

Effects of gamma irradiation on the worm survival and chromosomal aberration of Clonorchis sinensis were studied. The metacercariae irradiated with various amounts of gamma radiation (ranging from 5 Gy to 50 Gy) were fed to rats, and the effects were compared with those of non-irradiated controls. Recovery rates of adult worms in irradiated groups were reduced gradually as increasing of the irradiation doses. No worm was recovered from rats which were fed with 50 Gy irradiated metacercariae. The chromosome number was 2n = 56 in all worms from all experimental groups. However, the groups irradiated with 20 Gy, 25 Gy or 30 Gy showed variations in the chromosome number, depending on different cells in the same individual. Radiation doses used in this study did not appear to induce chromosome aberrations, however, irradiation with 30 Gy showed slightly reduced chromosome size.

Alteraciones cromosómicas en linfocitos humanos inducidas por rayos X / Human lymphocyte chromosome changes induced by x-rays

With the aim of determine and characterize chromosomal alterations in human lymphocytes induced by x-rays, an experimental study was performed with auto-control in four healthy donors (two males and two females). Peripheral blood was drawn, and divided in six aliquots: five of them were irradiated with 0.5, 1, 2, 3 and 4 Gy using a linear accelerator and one aliquot was used as control for each donor. The chromosomal analysis was carried out with the "G banding technique". It was observed that as the irradiation doses were raised, the abnormal metaphases and frequency of chromosomal alterations increased as well. The majority of chromosomal alterations were of the structural type, of which the most relevant ones were translocations, fragile sites and deletions. A significant difference was observed between the exposed and non-exposed groups with regard to the irradiation doses and the apparition of chromosomal alterations (p < 0.05). Chromosome 1 was more frequently involved in structural chromosomal alterations, followed by chromosomes 3, 10, 6, 7 and 9. The results presented in this study indicate that chromosomal alterations induced by acute exposure to x-rays increase linearly once the irradiation doses are raised. Therefore, the cytogenetic analysis can be considered as a useful tool for the control of the absorbed radiation dose and its biologicals effects in men.

Efecto de la fototerapia sobre los cromosomas de recién nacidos ictéricos / Effect of phototherapy on the chromosomes of newborn infants with jaundice

En el presente trabajo se comparó la fecuencia de aberraciones cromosómicas (AC) y de intercambios de cromátides hermanas (ICH) en los linfocitos de ocho neonatos inctéricos antes u después del tratamiento con fototerapia con el objeto de identificar el posible daño cromosómico. En cada paciente se analizaron 100 mitosis en primera división celular para el registro de las AC y 25 en segunda división para el registró de ICH tanto en los cultivos antes del tratamiento como en los posteriores al mismo. Los resultados no mostraron diferencias significativas en la frecuencia del AC y de ICH antes y después de la fototerapia. Se discute como a pesar de las evidencias in vitro de daño al ADN por la luz de fototerapia sobre todo en presencia de bilirrubina, no se ha demostrado daño cromosómico in vivo

A síndrome de Down: aspectos etiológicos / Down's syndrome: etiological aspects

Trabalho de revisäo que aborda aspectos referentes à etiologia do mongolismo e analisa, principalmente, os fatores que levam a näo-disjunçäo cromossômica nos pais, enfatizando a defasagem entre ovulaçäo e fecundaçäo, bem como a distribuiçäo sazonal da Síndrome de Down

Genetic X-radiation Damage to Drosophila Germ Cells under Different Conditions

Drosophila melanogaster (Oregon-R, Oak Ridge strain) males, 19 to 21 hours old, were X-rayed with a total dose of 1000r. or 3000 r. given in two equal fractions of 500 r. or 1500 r. at a dose rate of 500r. per minute, except for Experiment #2 in which they were given a single dose of 1000 r. at 24 +/- 1 degree C in several gas environments, with a time interval of 40 minutes between the two doses. At each Change of gas(es),the system was evacuated to remove all gases, then Hushed with helium for 1 minute. Tests using CO were carried out in the dark and the others m the light, both at 1 atmosphere of the gas or gas mixture. In order to study the genetic radiation damage and its modification by several gases the frequencies of dominant lethals and translocations induced in cells which were in different stages of spermatogenesis were scored using seven sequential 2-day mating over a two-week test period. Data are prtsented which indicate that: 1) The frequency of dominant lethals increased from sperm to spermatids and meiotic cells, then decreased in spermatogonial cells which were the least susceptible to X-rays. 2) The cycle of damage for dominant lethals is similar to that for translocations, but does not coincide with it completely, and the peaks of damage for both are located in the early postmeiotic stages, and the cycle of frequencies of translocations coincides with that of percentages of sterility of F1 the coincidence frequencies between translocations and the sterility demonstrates that the mechanisms of damage for both are related, at least in part. 3) The NO effect on sperm and late spermatids is more drastic than the oxygen effect, but a major fraction of the effect is to cause the death of the sperm. 4) The carbon monoxide (CO) during radiation increase genetic damage above the other gases tested, and it is possible to conclude that the duration(s) of 4 minutes of gases in post-treatments is too short to modify the damage. 5) There are few (or no) translocations recovered from premeiotic cells. 6) The Y-chromosome was involved in 10.8% of total breaks, or about 1/4 as frequently as the two autosomes tested, and chromosomes 2 and 3 equally participated in an interchange.