RESUMEN
Human exposure to ionizing radiation has increased over time, mainly due to medical applications, occupational and environmental exposure, as well as accidents involving radioactive materials. In September 1987, an accident with 137Cesium occurred in Goiânia city, Brazil; the accident started with the removal of a 50.9-TBq 137Cesium source from an abandoned radiotherapy unit. Among the radiation-exposed victims, at least 50 individuals showed symptoms of whole-body and local acute irradiation, and also external or internal contamination. In this report, the purpose was to review and summarize the main results of cytogenetic studies carried out with victims of 137Cesium, for blood collection performed shortly after the accident, and following several years post-exposure. The importance of dose estimates by biological dosimetry is highlighted, and also several lessons that were learned from the initial to follow-up (7-10â¯years after the accident) studies, mainly by applying the fluorescence in situ hybridization (FISH) method. A relevant aspect discussed on the basis of the results obtained in those studies refers to the incidence of chromosomal translocations, which were directly compared to the initial frequencies of dicentrics that were previously used to estimate the absorbed doses. In general, translocation frequencies were two to three times lower than the dicentric frequencies, and the differences were dose-dependent. Furthermore, regarding attempts to perform retrospective dosimetry (10 years post-accident), the dose estimates using translocation frequencies for victims of 137Cesium indicate the feasibility of this approach only for low level exposure (below 0.5â¯Gy), while for higher doses there are some limitations, and the requirement to apply appropriate correction factors, which were discussed on the basis of literature data. Apart of this, in general terms, important aspects to be mentioned refer to the need for better care and control of radioactive devices, as well as adequate education programs for professionals and also the population.
Asunto(s)
Radioisótopos de Cesio/efectos adversos , Exposición a la Radiación/efectos adversos , Radiación Ionizante , Liberación de Radiactividad Peligrosa , Radiometría/métodos , Translocación Genética/efectos de la radiación , Humanos , Dosis de Radiación , Estudios RetrospectivosRESUMEN
Healthy radio-exposed individuals who received low levels of Cesium-137 radiation during the accident that occurred in Goiânia in 1987, their families and controls were tested for the detection of t(14;18)-rearranged B cells in peripheral blood by using a highly sensitive, real-time quantitative PCR method. The chromosomal translocation t(14;18)(q32;q21) is characteristic of follicular lymphoma and is a frequent abnormality observed in other types of non-Hodgkin's lymphoma. This translocation leads to constitutive activation of the BCL2 oncogene by the enhancers of the immunoglobulin heavy-chain locus. In healthy individuals, the same translocation may also be found in a small fraction of peripheral blood lymphocytes, and positive cells might serve as an indicator for environmental exposure to carcinogens and possibly correlate with the cumulative risk of developing t(14;18)- positive non-Hodgkin's lymphoma. Twenty healthy radio-exposed individuals, 10 relatives and 10 non-exposed healthy individuals were tested for the detection of this translocation. Only 1 non-exposed individual was positive for the chromosomal translocation, and healthy radio-exposed individuals presented lower levels of cells bearing the BCL2/J(H) rearrangement when compared to the levels of the patients with follicular lymphoma before treatment. However, evaluation of more cells would be required to confirm the total absence of circulating cells bearing BCL2/J(H) rearrangement.
Asunto(s)
Radioisótopos de Cesio/efectos adversos , Genes bcl-2 , Liberación de Radiactividad Peligrosa , Translocación Genética/efectos de la radiación , Adulto , Linfocitos B/efectos de la radiación , Brasil , Línea Celular , Cromosomas Humanos Par 14/efectos de la radiación , Cromosomas Humanos Par 18/efectos de la radiación , Exposición a Riesgos Ambientales/efectos adversos , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Linfoma Folicular/etiología , Linfoma Folicular/genética , Linfoma no Hodgkin/etiología , Linfoma no Hodgkin/genética , Neoplasias Inducidas por Radiación/etiología , Neoplasias Inducidas por Radiación/genéticaRESUMEN
The aim of the present study was to investigate whether chromosome 16p presents breakpoint regions susceptible to radiation-induced rearrangements. The frequencies of translocations were determined by fluorescence in situ hybridization (FISH) using cosmid probes C40 and C55 mapping on chromosome 16p, and a chromosome 16 centromere-specific probe (pHUR195). Peripheral lymphocytes were collected from normal individuals and from seven victims of 137Cs in the Goiania (Brasil) accident (absorbed doses: 0.8-4.6 Gy) 10 years after exposure. In vitro irradiated lymphocytes (3 Gy) were also analyzed. The mean translocation frequency/cell obtained for the 137Cs exposed individuals was 2.4-fold higher than the control value (3.6 x 10(-3) +/- 0.001), and the in vitro irradiated lymphocytes showed a seven-fold increase. The genomic translocation frequencies (FGs) were calculated by the formula Fp = 2.05 fp(1-fp)FG (Lucas et al., 1992). For the irradiated lymphocytes and victims of 137Cs, the FGs calculated on the basis of chromosome 16 were 2- to 8-fold higher than those for chromosomes 1, 4 and 12. Our results indicate that chromosome 16 is more prone to radiation-induced chromosome breaks, and demonstrate a non-random distribution of induced aberrations. This information is valuable for retrospective biological dosimetry in case of human exposure to radiation, since the estimates of absorbed doses are calculated by determining the translocation frequency for a sub-set of chromosomes, and the results are extrapolated to the whole genome, assuming a random distribution of induced aberrations. Furthermore, the demonstration of breakpoints on 16p is compatible with the reports about their involvement in neoplasias.
Asunto(s)
Cromosomas Humanos Par 16/genética , Cromosomas Humanos Par 16/efectos de la radiación , Reordenamiento Génico/efectos de la radiación , Linfocitos/efectos de la radiación , Adulto , Brasil/epidemiología , Células Cultivadas , Radioisótopos de Cesio/efectos adversos , Pintura Cromosómica/métodos , Femenino , Reordenamiento Génico/genética , Humanos , Hibridación Fluorescente in Situ/métodos , Linfocitos/química , Linfocitos/citología , Linfocitos/metabolismo , Masculino , Persona de Mediana Edad , Dosis de Radiación , Liberación de Radiactividad Peligrosa , Tiempo , Translocación Genética/efectos de la radiaciónRESUMEN
Electron spin resonance and fluorescence in situ hybridization were used to evaluate the dose to the finger of a worker who accidentally touched a radiotherapy 60Co therapy source in November 1995. In September 1999, the middle finger was amputated. We estimated the dose to the bone of the finger to be 6.4 +/- 0.5 Gy using the electron spin resonance additive dose method and a corrected dose of about 20 +/- 3 Gy could be inferred by translocation analysis in peripheral lymphocytes using the fluorescence in situ hybridization method. This retrospective dosimetry was performed for the victim 4 y after the accident, but the compatibility of the results obtained by physical and biological methods reinforce their validity, although in the case of partial-body exposure the biological method has limitations and demonstrates the need to find appropriate correction factors.
Asunto(s)
Huesos de la Extremidad Superior/efectos de la radiación , Radioisótopos de Cobalto/efectos adversos , Dedos/efectos de la radiación , Exposición Profesional/análisis , Monitoreo de Radiación/métodos , Radiometría/métodos , Adulto , Amputación Quirúrgica , Huesos de la Extremidad Superior/química , Células Cultivadas , Espectroscopía de Resonancia por Spin del Electrón/métodos , Traumatismos de los Dedos/etiología , Dedos/cirugía , Estudios de Seguimiento , Personal de Salud , Humanos , Hibridación Fluorescente in Situ/métodos , Técnicas In Vitro , Linfocitos/sangre , Linfocitos/patología , Linfocitos/efectos de la radiación , Masculino , Traumatismos por Radiación/etiología , Monitoreo de Radiación/instrumentación , Liberación de Radiactividad Peligrosa , Estudios Retrospectivos , Sensibilidad y Especificidad , Translocación Genética/efectos de la radiaciónRESUMEN
The objective of this study was to standardize an induction strategy of chromosome aberrations in maize inbred line L-869. Pollen grains irradiated with 0, 36 and 72 Gy were used for fertilization. Resulting seeds were planted in a greenhouse to assess the number of abnormal meiotic cells. Germination, height, sterility and mortality were verified. Cells with delayed separation of chromosomes, translocation, deficiency, abnormal pairing, later condensation and anaphase bridges were observed. The number of abnormalities increased as the dosage increased but chromosome aberration types were the same regardless of the dosages used. Various chromosome-altered plants were obtained without viability loss
Asunto(s)
Aberraciones Cromosómicas/efectos de la radiación , Meiosis/efectos de la radiación , Polen/genética , Polen/efectos de la radiación , Zea mays/genética , Zea mays/efectos de la radiación , Flores/genética , Flores/efectos de la radiación , Rayos gamma , Germinación/efectos de la radiación , Translocación Genética/efectos de la radiaciónRESUMEN
The radiation accident in focus here occurred in a section of Goiânia (Brazil) where more than a hundred individuals were contaminated with 137Cesium on September 1987. In order to estimate the absorbed radiation doses, initial frequencies of dicentrics and rings were determined in 129 victims [A.T. Ramalho, PhD Thesis, Subsidios a tecnica de dosimetria citogenetica gerados a partir da analise de resultados obtidos com o acidente radiologico de Goiânia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil, 1992]. We have followed some of these victims cytogenetically over the years seeking for parameters that could be used as basis for retrospective radiation dosimetry. Our data on translocation frequencies obtained by fluorescence in situ hybridization (FISH) could be directly compared to the baseline frequencies of dicentrics available for those same victims. Our results provided valuable information on how precise these estimates are. The frequencies of translocations observed years after the radiation exposure were two to three times lower than the initial dicentrics frequencies, the differences being larger at higher doses (>1 Gy). The accuracy of such dose estimates might be increased by scoring sufficient amount of cells. However, factors such as the persistence of translocation carrying lymphocytes, translocation levels not proportional to chromosome size, and inter-individual variation reduce the precision of these estimates.
Asunto(s)
Radioisótopos de Cesio/efectos adversos , Aberraciones Cromosómicas/genética , Hibridación Fluorescente in Situ , Liberación de Radiactividad Peligrosa , Brasil , Células Cultivadas , Femenino , Estudios de Seguimiento , Rayos gamma/efectos adversos , Humanos , Linfocitos/efectos de la radiación , Masculino , Radiometría , Estudios Retrospectivos , Translocación Genética/efectos de la radiaciónRESUMEN
Con el fin de mejorar la producción animal se ha utilizado el análisis cromosómico de los reproductores. Esta técnica permitió demostrar, por primera vez en Venezuela, la existencia de la translocación Robertsoniana 1/29 (Rb 1/29) en toros Criollos Río Limón de la Estación Experimental Guárico (FONAIAP). El presente estudio fué realizado en la misma estación experimental, evaluando cromosómicamente el total de vacas Criollas Río Limón destinadas a la reproducción, con el propósito de establecer la presencia de anomalías cromosómicas en hembras. Se utilizó la técnica del cultivo de linfocitos de sangre periférica estimulados con mitógeno, para obtener placas metafásicas, que fueron teñidas con Giemsa y marcadas en bandeo G. De las 21 vacas analizadas se obtuvo una portadora de la Rb 1/29 (4,8 por ciento) en condición de heterocigosis. Esta incidencia en comparación con el 16,6 por ciento obtenida en 30 toros, indica que la selección por eficacia reproductiva aplicada al rebaño durante aproximadamente 30 años, elimina con mayor eficacia a las vacas portadoras de la translocación. Así como es imprescindible evaluar cromosómicamente a los toros destinados a la reproducción, también es importante evaluar a vacas reproductoras jóvenes, ya que la evaluación citogenética elimina más rápidamente la dispersión de anomalías cromosómicas que la selección por eficacia reproductiva
Asunto(s)
Animales , Bovinos , Aberraciones Cromosómicas/diagnóstico , Cromosomas/genética , Translocación Genética/efectos de la radiaciónRESUMEN
The response of fully mature motile sperm and late spermatids when challenged with X-radiation at 0 degrees C has been studied in sex-linked recessive lethals, II-III translocations and dominant lethality experiments. At 0 degrees C a significant increase in both mutagenic and clastogenic damage was detected compared to that obtained at 24 degrees C. Furthermore, the results of experiments performed with different postirradiation temperatures demonstrate that the low temperature during irradiation was the sole factor responsible for the observed increase. In the recessive lethal and translocation tests the response of late spermatids was higher than that shown by motile spermatozoa. As a whole, the results, which are rather similar to data reported on the effect of irradiation in oxygen of the same cell stages, suggest that the low temperature acted as a dose-modifying factor.
Asunto(s)
Frío , Drosophila melanogaster/genética , Drosophila melanogaster/efectos de la radiación , Espermátides/efectos de la radiación , Espermatozoides/efectos de la radiación , Animales , Distribución de Chi-Cuadrado , Genes Dominantes , Genes Letales , Genes Recesivos , Ligamiento Genético , Masculino , Mutagénesis , Dosis de Radiación , Cromosomas Sexuales/efectos de la radiación , Translocación Genética/efectos de la radiaciónRESUMEN
Centromeric breaks and the dissociation of Robertsonian translocations have been regarded as the possible cause of a few reported cases of mosaicism. In a previous study we suggested that the dissociative phenomenon is influenced by an instability of the point of fusion, when it is located on a heterochromatic region, which appears to be a preferential mitomycin C (MMC) breakpoint. In this study lymphocytes from 6 robertsonian translocation carriers were treated with gamma rays. In one case who was a mosaic, the MMC induced a statistically significant increase in the number of cells with the dissociation. In the remaining cases, centromeric breaks or complete fissions were observed in 1.8% of the cells. In addition, the analysis of the distribution of breakage points on heterochromatic or euchromatic regions showed that almost 50% of the breaks on translocation chromosomes were located on pericentromeric heterochromatin. We postulate that the dissociation which occurs in robertsonian translocations may be caused by instability of the point of fusion since it is located on a heterochromatic region, susceptible to breakage by clastogenic agents such as MMC and gamma rays.
Asunto(s)
Translocación Genética/efectos de la radiación , Rayos gamma , Humanos , CariotipificaciónRESUMEN
The combined effects of mitomycin C (MMC) and thio-tepa (TT) with gamma-ray doses of 5 and 9 Gy on mouse stem cells were studied using the spermatocyte test. Both chemicals induced very low yields of translocations after single treatments. In combined treatments with a dose of 5 Gy, a subadditive effect of MMC and an additive effect of TT were found. Combined with a dose of 9 Gy the compounds potentiated the effect of radiations. Up to now, most of the chemicals tested have shown additive effects when combined with doses of the ascending part of the dose-response curve and potentiating effects when combined with doses of its descending part. This has been considered additional confirmation of the concept that depletion of any kind of spermatogonia is sufficient to modify the genetic response of stem cells. However, the subadditive and additive responses found could be considered evidence that common biological mechanisms can modulate the response to combined treatments of chemicals and ionizing radiations.
Asunto(s)
Rayos gamma , Mitomicinas/toxicidad , Radiación Ionizante , Espermatogonias , Espermatozoides , Tiotepa/toxicidad , Translocación Genética , Animales , Relación Dosis-Respuesta a Droga , Relación Dosis-Respuesta en la Radiación , Masculino , Ratones , Ratones Endogámicos BALB C , Mitomicina , Espermatogonias/efectos de los fármacos , Espermatogonias/efectos de la radiación , Espermatozoides/efectos de los fármacos , Espermatozoides/efectos de la radiación , Translocación Genética/efectos de los fármacos , Translocación Genética/efectos de la radiaciónRESUMEN
The induction of reciprocal translocations in mouse germ cells by combined treatments with chemicals and ionizing radiations has been studied. Male mice were intraperitoneally injected with doses of 5 or 10 mg/kg of adriamycin (ADR) and irradiated with doses of 5 or 9 Gy of gamma-rays 24 h later. Three types of response were found after analyzing diakinesis-metaphase I multivalent configurations: potentiation, with the dose of 5 mg/kg of ADR plus 9 Gy; subadditivity, with the dose of 5 mg/kg of ADR plus 5 Gy; and additivity, with the dose of 10 mg/kg of ADR plus 5 or 9 Gy. According to these results, the subadditive effect observed with the lower dose of ADR plus 5 Gy cannot be explained under the assumption that depletion of any kind of spermatogonia is sufficient for modifying the chromosomal response of stem cells to ionizing radiations. The role of DNA repair mechanisms modulating the response of spermatogonial cells to combined treatments is discussed under the assumption that some repair mechanisms can be triggered by treatment with a low dose of a chemical and these repair mechanisms can reduce cell mortality. Consequently, a higher frequency of more radioresistant cells can survive.
Asunto(s)
Doxorrubicina/toxicidad , Rayos gamma , Radiación Ionizante , Espermatogonias , Espermatozoides , Translocación Genética , Animales , Relación Dosis-Respuesta a Droga , Relación Dosis-Respuesta en la Radiación , Masculino , Ratones , Ratones Endogámicos BALB C , Espermatogonias/efectos de los fármacos , Espermatogonias/efectos de la radiación , Espermatozoides/efectos de los fármacos , Espermatozoides/efectos de la radiación , Translocación Genética/efectos de los fármacos , Translocación Genética/efectos de la radiaciónRESUMEN
The effects of glyoxal and of glyoxal pretreatments on radiation-induced genetic damage were investigated in Drosophila melanogaster mature sperm, by means of sex-linked recessive and dominant lethality, reciprocal translocation and chromosome loss tests. In addition, the possible mutagenic effect of glyoxal was assessed in postmeiotic cells up to 7 days after treatment. The results obtained show: (1) the frequencies of recessive lethals after glyoxal treatment were within control values, (2) no clastogenic effect of glyoxal was observed, (3) glyoxal pretreatment did not modify the frequency of recessive lethals induced by X-rays, (4) after pretreatment with glyoxal a consistent, though not significant, increase was seen in the frequency of reciprocal translocations in 3 replicate experiments, (5) the yield of dominant lethals and of complete and partial chromosome loss induced by radiation was significantly increased by pretreatments with glyoxal. It is suggested that the increase of the frequency of genetic endpoints resulting from chromosome breakage, when glyoxal was administered prior to irradiation, could be ascribed to: (a) a sensitizing action of glyoxal to the clastogenic effect of ionizing radiation; (b) the formation of reactive species by the interaction of glyoxal with radiation; and/or (c) interference of glyoxal with the normal handling of radiation-induced lesions in mature postmeiotic male cells.
Asunto(s)
Aldehídos/farmacología , Daño del ADN , ADN/efectos de la radiación , Glioxal/farmacología , Animales , Aberraciones Cromosómicas , ADN/efectos de los fármacos , Drosophila melanogaster , Genes Letales , Pruebas de Mutagenicidad , Mutación/efectos de los fármacos , Mutación/efectos de la radiación , Translocación Genética/efectos de los fármacos , Translocación Genética/efectos de la radiaciónRESUMEN
The effect of bleomycin (BLM) on mouse stem cells has been analysed using the spermatocyte test. The dose-response relationships after treatment with doses of 20, 40 and 60 mg/kg of the compound as well as the combined effect of BLM and gamma-rays and BLM and thio-tepa (TT) were studied. A positive, significant correlation between the dose of BLM and the frequency of translocations was found. Two different responses were found when the yields of translocations induced after combined treatments, separated by a lapse of 24 h, were compared with the sum of translocation frequencies induced after the corresponding single treatments: (1) Potentiation, in the treatments with 1 Gy plus 9 Gy and 60 mg/kg of BLM plus 9 Gy; (2) additivity, in the treatments with 60 mg/kg of BLM plus 1 Gy, 1 Gy plus 60 mg/kg of BLM, and 0.2 mg of TT plus 60 mg/kg of BLM. In mice irradiated with 1 Gy plus 9 Gy and mice treated with 60 mg/kg of BLM plus 9 Gy, similar translocation yields were found. The potentiating effect of BLM is similar to that obtained with non-radiomimetic compounds such as triethylenemelamine, cyclophosphamide and adriamycin. These results are discussed taking into account the hypothesis of germ cell selection, and the dose of radiation employed.