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1.
Int J Radiat Biol ; 96(6): 748-758, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32149567

RESUMEN

Purpose: Simple, rapid and high-throughput dose assessment is critical for clinical diagnosis, treatment and emergency intervention in a large-scale radiological accident. The goal of this study is to screen and identify new ionizing radiation-responsive protein biomarkers in rat plasma.Materials and methods: Sprague-Dawley rats were exposed to single doses of 0, 1, 3, 5 Gy of Cobalt-60 γ-rays total body irradiation at a dose rate of 1 Gy/min. The tandem mass tag labeling (TMT) combined with liquid chromatography mass spectrometry (LC-MS/MS) approach was used to screen the differentially expressed proteins in rat plasma collected at 1, 3, 5 and 7 days post-irradiation. Bioinformatics analysis was conducted to explore the biological functions of these proteins. The expression levels of candidate radiation-sensitive protein biomarkers were confirmed using enzyme-linked immune-sorbent assay (ELISA).Results: A total of 503 differentially expressed proteins were identified. Most of these proteins were implicated in immune response, phagocytosis and signal transduction following ionizing radiation. Five up-regulated proteins including alpha-2-macroglobulin (A2m), chromogranin-A (CHGA), glutathione pertidase 3 (GPX3), clusterin (Clu) and ceruloplasmin (Cp) were selected for ELISA analysis. It was found that the expression levels of A2m, CHGA and GPX3 protein were increased in a dose-dependent manner at 1, 3 and 5 days after irradiation.Conclusion: Proteomics analysis revealed radiation-induced differentially expressed proteins in rat plasma. Our results suggested that A2m, CHGA, GPX3 protein expressions alterations in rat plasma may have potential as biomarkers to evaluate radiation exposure.


Asunto(s)
Proteínas Sanguíneas/metabolismo , Rayos gamma/efectos adversos , Regulación de la Expresión Génica/efectos de la radiación , Animales , Biomarcadores/sangre , Proteínas Sanguíneas/genética , Ontología de Genes , Mapas de Interacción de Proteínas/efectos de la radiación , Ratas , Ratas Sprague-Dawley
2.
Radiat Res ; 192(4): 399-409, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31373872

RESUMEN

In a large-scale radiological incident, rapid and high-throughput biodosimetry would be needed. Gene expression-based biodosimetry is a promising approach to determine the dose received after radiation exposure. We previously identified 35 candidate genes as biodosimetry markers based on a systematic review. The goal of the current study was to establish and validate a specific gene expression-based radiological biodosimetry using a panel of highly radioresponsive genes in human peripheral blood for improving the accuracy of dose estimation. Human peripheral blood samples from 30 adult donors were irradiated to 0, 0.5, 1, 2, 3, 4, 6 and 8 Gy with 60Co γ rays at a dose rate of 1 Gy/min. We examined the expression patterns of candidate genes using real-time polymerase chain reaction (qRT-PCR) at 6, 12, 24 and 48 h postirradiation. Stepwise regression analysis was employed to develop the gene expression-based dosimetry models at each time point. Samples from another 10 healthy donors (blind samples) and four total-body irradiated (TBI) patients were used to validate the radiation dosimetry models. We observed significant linear dose-response relationships of CDKN1A, BAX, MDM2, XPC, PCNA, FDXR, GDF-15, DDB2, TNFRSF10B, PHPT1, ASTN2, RPS27L, BBC3, TNFSF4, POLH, CCNG1, PPM1D and GADD45A in human peripheral blood at the various time points. However, the expression levels of these genes were affected by inter-individual variations and gender. We found that the gender-dependent regression models could explain 0.85 of variance at 24 h postirradiation and could also accurately estimate the absorbed radiation doses with dose range of 0-5 Gy, in human peripheral blood samples irradiated ex vivo and from TBI patients, respectively. This study demonstrates that developing gender-specific biodosimetry based on a panel of highly radioresponsive genes may help advance the application of gene expression signature for dose estimation in the event of a radiological accident or in clinical treatment.


Asunto(s)
Sangre/metabolismo , Sangre/efectos de la radiación , Radiometría/métodos , Caracteres Sexuales , Transcriptoma/efectos de la radiación , Relación Dosis-Respuesta en la Radiación , Femenino , Humanos , Masculino , Modelos Biológicos , Factores de Tiempo
3.
Int J Mol Sci ; 20(7)2019 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-30965614

RESUMEN

Luteinizing hormone (LH), a pituitary gonadotropin, coupled with LH receptor (LHR) is essential for the regulation of the gonadal maturation in vertebrates. Although LH homolog has been detected by immunocytochemical analysis, and its possible role in ovarian maturation was revealed in decapod crustacean, so far there is no molecular evidence for the existence of LHR. In this study, we cloned a novel LHR homolog (named EsLHR) from the Chinese mitten crab Eriocheir sinensis. The complete sequence of the EsLHR cDNA was 2775bp, encoding a protein of 924 amino acids, sharing 71% amino acids identity with the ant Zootermopsis nevadensis LHR. EsLHR expression was found to be high in the ovary, while low in testis, gill, brain, and heart, and no expression in the thoracic ganglion, eye stalk, muscle, and hepatopancreas. Quantitative PCR revealed that the expression level of EsLHR mRNA was significantly higher in the ovaries in previtellogenic (Pvt), late vitellogenic (Lvt), and germinal vesicle breakdown (GVBD) stages than that in the vitellogenic (Mvt) and early vitellogenic (Evt) stages (P < 0.05), and, the highest and the lowest expression were in Lvt, and Evt, respectively. The strong signal was mainly localized in the ooplasm of Pvt oocyte as detected by in situ hybridization. The crab GnRH homolog can significantly induce the expression of EsLHR mRNA at 36 hours post injection in vivo (P < 0.01), suggesting that EsLHR may be involved in regulating ovarian development through GnRH signaling pathway in the mitten crab.


Asunto(s)
Braquiuros/metabolismo , Receptores de HL/metabolismo , Animales , Braquiuros/embriología , ADN Complementario/metabolismo , Femenino , Masculino , Ovario/embriología , Ovario/metabolismo , Reacción en Cadena de la Polimerasa , ARN Mensajero/metabolismo , Receptores de HL/genética , Testículo/embriología , Testículo/metabolismo
4.
Mutat Res Genet Toxicol Environ Mutagen ; 832-833: 29-34, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30057018

RESUMEN

Baseline nucleoplasmic bridges (NPB) vary widely in the general population from different regions in the same country or from different countries. The baseline NPB level in the normal Chinese population and the factors affecting the baseline and radiation-induced NPB levels have not been explored yet. The cytokinesis-block micronucleus cytome assay was conducted on the peripheral blood samples of 121 healthy individuals for the baseline NPB and 52 healthy individuals for the 2 Gy γ-ray-induced NPB level. The effects of age and gender on the baseline NPB and 2 Gy γ-ray-induced NPB level were evaluated. The overall baseline NPB in the peripheral blood lymphocytes of 121 healthy adults from the general population in China was 0.46 ±â€¯0.20 per 1000 binucleated (BN) cells. The overall baseline NPB in males (0.56 ±â€¯0.15 per 1000 BN cells) was higher than that in females (0.36 ±â€¯0.22 per 1000 BN cells, P < 0.05). The effect of age on the baseline NPB was not significant, except for females in the 40-year age group. The overall 2 Gy γ-ray-induced NPB frequency for male donors was lower than that for female donors (P < 0.01). No evident trend of the radiation-induced NPB level with increasing age was observed for both genders. For the baseline micronucleus (MN) and radiation-induced MN levels, the effects of gender and age were confirmed. Therefore, the gender of donors affects the baseline and radiation-induced levels of NPB and MN. In addition, the effect of the age of the donors on the baseline and radiation-induced NPB levels showed no clear pattern and needed to be further investigated.


Asunto(s)
Núcleo Celular/efectos de la radiación , Radioisótopos de Cobalto , Daño del ADN , Rayos gamma , Linfocitos/efectos de la radiación , Micronúcleos con Defecto Cromosómico/efectos de la radiación , Pruebas de Micronúcleos/métodos , Adulto , Factores de Edad , Anciano , China , Citocinesis , Femenino , Voluntarios Sanos , Humanos , Linfocitos/metabolismo , Masculino , Persona de Mediana Edad , Factores Sexuales , Adulto Joven
5.
Radiat Environ Biophys ; 57(3): 215-222, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29774413

RESUMEN

Chromosome damage is related to DNA damage and erroneous repair. It can cause cell dysfunction and ultimately induce carcinogenesis. Histone acetylation is crucial for regulating chromatin structure and DNA damage repair. Ionizing radiation (IR) can alter histone acetylation. However, variations in histone acetylation in response to IR exposure and the relationship between histone acetylation and IR-induced chromosome damage remains unclear. Hence, this study investigated the variation in the total acetylation levels of H3 and H4 in human lymphocytes exposed to 0-2 Gy 60Co γ-rays. Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase (HDAC) inhibitor, was added to modify the histone acetylation state of irradiated cells. Then, the total acetylation level, enzyme activity, dicentric plus centric rings (dic + r) frequencies, and micronucleus (MN) frequencies of the treated cells were analyzed. Results indicated that the acetylation levels of H3 and H4 significantly decreased at 1 and 24 h, respectively, after radiation exposure. The acetylation levels of H3 and H4 in irradiated groups treated with SAHA were significantly higher than those in irradiated groups that were not treated with SAHA. SAHA treatment inhibited HDAC activity in cells exposed to 0-1 Gy 60Co γ-rays. SAHA treatment significantly decreased dic + r/cell and MN/cell in cells exposed to 0.5 or 1.0 Gy 60Co γ-rays relative to that in cells that did not receive SAHA treatment. In conclusion, histone acetylation is significantly affected by IR and is involved in chromosome damage induced by 60Co γ-radiation.


Asunto(s)
Cromosomas Humanos/genética , Radioisótopos de Cobalto/efectos adversos , Rayos gamma/efectos adversos , Histonas/metabolismo , Linfocitos/efectos de la radiación , Acetilación/efectos de los fármacos , Acetilación/efectos de la radiación , Línea Celular , Inhibidores de Histona Desacetilasas/farmacología , Humanos , Ácidos Hidroxámicos/farmacología , Linfocitos/citología , Linfocitos/efectos de los fármacos , Linfocitos/metabolismo , Vorinostat
6.
Biomed Environ Sci ; 30(11): 834-840, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29216961

RESUMEN

The aim of the present study is to analyze the global research trend of radiation-responsive genes and identify the highly reproducible radiation-responsive genes. Bibliometric methods were applied to analyze the global research trend of radiation-responsive genes. We found 79 publications on radiation-responsive genes from 2000 to 2017. A total of 35 highly reproducible radiation-responsive genes were identified. Most genes are involved in response to DNA damage, cell proliferation, cell cycle regulation, and DNA repair. The p53 signal pathway was the top enriched pathway. The expression levels of 18 genes in human B lymphoblastoid cell line (AHH-1) cells were significantly up-regulated in a dose-dependent manner at 24 h after exposure to 0-5 Gy 60Co γ-ray irradiation. Our results indicate that developing a gene expression panel with the 35 high reproducibility radiation-responsive genes may be necessary for qualitative and quantitative assessment after exposure.


Asunto(s)
Regulación de la Expresión Génica/efectos de la radiación , Radiometría/métodos , Relación Dosis-Respuesta en la Radiación , Perfilación de la Expresión Génica , Humanos , Reproducibilidad de los Resultados , Regulación hacia Arriba/efectos de la radiación
7.
Mol Med Rep ; 15(6): 3599-3606, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28440431

RESUMEN

The identification of rapid, sensitive and high­throughput biomarkers is imperative in order to identify individuals harmed by radiation accidents, and accurately evaluate the absorbed doses of radiation. DNA microarrays have previously been used to evaluate the alterations in growth/differentiation factor 15 (GDF15) gene expression in AHH­1 human lymphoblastoid cells, following exposure to γ­rays. The present study aimed to characterize the relationship between the dose of ionizing radiation and the produced effects in GDF­15 gene expression in AHH­1 cells and human peripheral blood lymphocytes (HPBLs). GDF­15 mRNA and protein expression levels following exposure to γ­rays and neutron radiation were assessed by reverse transcription­quantitative polymerase chain reaction and western blot analysis in AHH­1 cells. In addition, alterations in GDF­15 gene expression in HPBLs following ex vivo irradiation were evaluated. The present results demonstrated that GDF­15 mRNA and protein expression levels in AHH­1 cells were significantly upregulated following exposure to γ­ray doses ranging between 1 and 10 Gy, regardless of the dose rate. A total of 48 h following exposure to neutron radiation, a dose­response relationship was identified in AHH­1 cells at γ­ray doses between 0.4 and 1.6 Gy. GDF­15 mRNA levels in HPBLs were significantly upregulated following exposure to γ­ray doses between 1 and 8 Gy, within 4­48 h following irradiation. These results suggested that significant time­ and dose­dependent alterations in GDF­15 mRNA and protein expression occur in AHH­1 cells and HPBLs in the early phases following exposure to ionizing radiation. In conclusion, alterations in GDF­15 gene expression may have potential as a biomarker to evaluate radiation exposure.


Asunto(s)
Regulación de la Expresión Génica/efectos de la radiación , Factor 15 de Diferenciación de Crecimiento/genética , Linfocitos/metabolismo , Linfocitos/efectos de la radiación , Radiación Ionizante , Adulto , Línea Celular Tumoral , Relación Dosis-Respuesta en la Radiación , Rayos gamma , Factor 15 de Diferenciación de Crecimiento/metabolismo , Humanos , Masculino , Neutrones , ARN Mensajero/genética , ARN Mensajero/metabolismo
8.
Artículo en Inglés | MEDLINE | ID: mdl-27542714

RESUMEN

Many studies have investigated exposure biomarkers for high dose radiation. However, no systematic study on which biomarkers can be used in dose estimation through premature chromosome condensation (PCC) analysis has been conducted. The present study aims to screen the high-dose radiation exposure indicator in calyculin A-induced PCC. The dose response of multiple biological endpoints, including G2/A-PCC (G2/M and M/A-PCC) index, PCC ring (PCC-R), ratio of the longest/shortest length (L/L ratio), and length and width ratio of the longest chromosome (L/B ratio), were investigated in calyculin A-induced G2/A-PCC spreads in human peripheral blood lymphocytes exposed to 0-20Gy (dose-rate of 1Gy/min) cobalt-60 gamma-rays. The G2/A-PCC index was decreased with enhanced absorbed doses of 4-20Gy gamma-rays. The G2/A PCC-R at 0-12Gy gamma-rays conformed to Poisson distribution. Three types of PCC-R were scored according to their shape and their solidity or hollowness. The frequencies of hollow PCC-R and PCC-R including or excluding solid ring in G2/A-PCC spreads were enhanced with increased doses. The length and width of the longest chromosome, as well as the length of the shortest chromosome in each G2/M-PCC or M/A-PCC spread, were measured. All L/L or L/B ratios in G2/M-PCC or M/A-PCC spread increased with enhanced doses. A blind test with two new irradiated doses was conducted to validate which biomarker could be used in dose estimation. Results showed that hollow PCC-R and PCC-R including solid ring can be utilized for accurate dose estimation, and that hollow PCC-R was optimal for practical application.


Asunto(s)
Carcinógenos/toxicidad , Cromosomas/efectos de los fármacos , Rayos gamma/efectos adversos , Linfocitos/efectos de la radiación , Micronúcleos con Defecto Cromosómico/efectos de la radiación , Oxazoles/toxicidad , Adulto , Células Cultivadas , Cromosomas/efectos de la radiación , Radioisótopos de Cobalto , Relación Dosis-Respuesta a Droga , Relación Dosis-Respuesta en la Radiación , Humanos , Linfocitos/efectos de los fármacos , Masculino , Toxinas Marinas , Micronúcleos con Defecto Cromosómico/efectos de los fármacos
9.
Nat Prod Res ; 29(14): 1380-3, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25647513

RESUMEN

This work aimed to investigate benzophenanthridine from the roots of Zanthoxylum nitidum (Roxb.) DC. var. fastuosum How ex Huang for the first time. Thirteen benzophenanthridines were isolated, and our results of the cytotoxic activities indicated that compound 6 exhibited the best potency against A549, Hela, SMMC-7721 and EJ, with the IC50 values of 27.50, 37.50, 16.95 and 60.42 µM, respectively. Compounds 7 and 11 also showed strong cytotoxicity when tested against the four human cancer cell lines (A549, Hela, SMMC-7721 and EJ), while only compounds 12 and 13 displayed cytotoxicity in inhibiting BALL-1 proliferation among all the compounds. These results suggested that benzophenanthridines may become a valid alternative of potential basis for new anti-proliferative agents.


Asunto(s)
Alcaloides/farmacología , Benzofenantridinas/farmacología , Raíces de Plantas/química , Zanthoxylum/química , Línea Celular Tumoral/efectos de los fármacos , Humanos , Estructura Molecular
10.
Int J Radiat Biol ; 91(1): 71-80, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24991881

RESUMEN

PURPOSE: To identify new ionizing radiation (IR)-sensitive genes and observe the dose-effect of gene expression alteration (GEA) induced by IR. MATERIALS AND METHODS: Microarray was used to screen the differentially expressed genes in human lymphoblastoid cells (AHH-1) using three doses of (60)Co γ-rays (0.5-8 Gy at 1 Gy/min). Given that p53-inducible gene 3 (PIG3) was consistently upregulated, the GEA of PIG3 in AHH-1 cells and human peripheral blood lymphocytes (HPBL) induced by γ-rays (1 Gy/min) was measured at messenger RNA (mRNA) and protein levels. The GEA of PIG3 in AHH-1 cells exposed to neutron radiation (californium-252, 0.073 Gy/min) was also quantified. RESULTS: PIG3 was one of the seven differentially expressed genes found in the microarray analysis. The PIG3 mRNA and protein levels in AHH-1 cells were significantly increased from 1-10 Gy of γ-rays 8-72 h or 8-168 h after exposure, respectively. The enhancement was also observed in AHH-1 cells from 0.4-1.6 Gy of neutrons 48 h post-irradiation. The PIG3 mRNA levels (mRNA copy numbers) in HPBL were significantly increased from 1-8 Gy of γ-rays within 4-24 h post-irradiation, but the highest increase in signal-to-noise responsiveness is approximately two-fold, which was less than that of AHH-1 (approximately 20-fold). CONCLUSIONS: IR can upregulate the PIG3 gene expression in AHH-1 and HPBL in the early phase after exposure; however, the IR induced expression levels of PIG3 are greater in AHH-1 than HPBL.


Asunto(s)
Rayos gamma , Regulación de la Expresión Génica/efectos de la radiación , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Linfocitos/metabolismo , Linfocitos/efectos de la radiación , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo , Adulto , Línea Celular , Radioisótopos de Cobalto , Relación Dosis-Respuesta en la Radiación , Humanos , Masculino , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factores de Tiempo
11.
Molecules ; 19(12): 20128-38, 2014 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-25470278

RESUMEN

Schinifoline (SF), a 4-quinolinone derivative, was found in Zanthoxylum schinifolium for the first time. 4-Quinolinone moieties are thought to have cytotoxic activity and are often used as a tubulin polymerization inhibitors, heterogeneous enzyme inhibitors and antiplatelet agents. However, very little information respect to radiosensitization has focused on SF. This work aimed to investigate the radiosensitizing effect of SF on A549 cells. The cell viability results indicated cytotoxicity of SF on A549 cells, with IC50 values of 33.7 ± 2.4, 21.9 ± 1.9 and 16.8 ± 2.2 µg/mL, respectively, after 6, 12, 24 h treatment with different concentrations, and the 10% or 20% IC50 concentration during 12 h was applied in later experiments. The results of cell proliferative inhibition and clonogenic assay showed that SF enhanced the radiosensitivity of A549 cells when applied before 60Co γ-irradiation and this effect was mainly time and concentration dependent. The flow cytometric data indicated that SF treatment before the irradiation increased the G2/M phase, thus improving the radiosensitivity of A549, leading to cell apoptosis. This paper is the first study that describes the in vitro radiosensitising, cell cycle and apoptotic-inducing effects of schinifoline.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Quinolonas/farmacología , Fármacos Sensibilizantes a Radiaciones/farmacología , Zanthoxylum/química , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Puntos de Control del Ciclo Celular/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de la radiación , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Rayos gamma , Humanos , Quinolonas/química , Radiación Ionizante , Sesquiterpenos/farmacología , Ensayo de Tumor de Célula Madre
12.
Asian Pac J Cancer Prev ; 15(15): 6161-4, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25124591

RESUMEN

BACKGROUND: We have reported the radiation could activate STAT3, which subsequently promotes the invasion of A549 cells. We here explored the dose- and time-response of STAT3 to radiation and the effect of radiation on upstream signaling molecules. MATERIALS AND METHODS: A549 cells were irradiated with different doses of γ-rays. The expression of and nucleus translocation of p-STAT3 in A549 cells were detected by immunoblotting and immunofluorescence, respectively. The level of phosphorylated EGFR was also assessed by immunoblotting, and IL-6 expression was detected by real time PCR and ELISA. RESULTS: Radiation promoted the phosphorylation of STAT3 at Y705 in a dose- and time-dependent manner and nuclear translocation. The level of phosphorylated EGFR in A549 cells increased after radiation. In additional, the mRNA and protein levels of IL-6 in A549 cells were also up regulated by radiation. CONCLUSIONS: STAT3 is activated by radiation in a dose-and time-dependent manner, probably due to radiation-induced activation of EGFR or secretion of IL-6 in A549 cells.


Asunto(s)
Proliferación Celular/efectos de la radiación , Radioisótopos de Cobalto , Rayos gamma , Regulación Neoplásica de la Expresión Génica/efectos de la radiación , Neoplasias Pulmonares/radioterapia , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/efectos de la radiación , Western Blotting , Técnica del Anticuerpo Fluorescente , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Fosforilación/efectos de la radiación , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Transcripción STAT3/genética , Células Tumorales Cultivadas , Regulación hacia Arriba
13.
Artículo en Inglés | MEDLINE | ID: mdl-24246721

RESUMEN

The present study aims to evaluate the use of the fluorescence in situ hybridization (FISH) translocation assay for retrospective dose estimation of acute accidental exposure to radiation in the past. Reciprocal translocation analysis by FISH with three whole-chromosome probes was performed on normal peripheral blood samples. Samples were irradiated with 0-5Gy (60)Co γ-rays in vitro, and dose-effect curves were established. FISH-based translocation analyses for six accident victims were then performed, and biological doses were estimated retrospectively by comparison with the dose-effect curves. Reconstructed doses by FISH were compared with estimated doses obtained by analysis of di-centrics performed soon after exposure, or with dose estimates from tooth-enamel electron paramagnetic resonance (EPR) data obtained at the same time as the FISH analysis. Follow-up FISH analyses for an adolescent victim were performed. Results showed that dose-effect curves established in the present study follow a linear-quadratic model, regardless of the background translocation frequency. Estimated doses according to two dose-effect curves for all six victims were similar. FISH dose estimations of three adult victims exposed to accidental radiation less than a decade prior to analysis (3, 6, or 7 years ago) were consistent with those estimated with tooth-enamel EPR measurements or analyses of di-centrics. Estimated doses of two other adult victims exposed to radiation over a decade prior to analysis (16 or 33 years ago) were underestimated and two to three times lower than the values obtained from analysis of di-centrics or tooth-enamel EPR. Follow-up analyses of the adolescent victim showed that doses estimated by FISH analysis decrease rapidly over time. Therefore, the accuracy of dose estimates by FISH is acceptable only when analysis is performed less than 7 years after exposure. Measurements carried out more than a decade after exposure through FISH analysis resulted in underestimation of the biological doses compared with values obtained through analysis of di-centrics and tooth-enamel EPR.


Asunto(s)
Hibridación Fluorescente in Situ/métodos , Dosis de Radiación , Liberación de Radiactividad Peligrosa , Adolescente , Adulto , Células Cultivadas , Relación Dosis-Respuesta en la Radiación , Espectroscopía de Resonancia por Spin del Electrón , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
14.
Molecules ; 18(9): 10768-75, 2013 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-24005969

RESUMEN

Six compounds were isolated from the stems of Clausena lansium (Lour.) Skeels by repeated sillica gel column chromatography. Their chemical structures were elucidated on the basic of physicochemical and spectroscopic data. Among them, 8-geranyloxypsolaren (3) and 2-methoxy-1-(3-methyl-buten-1-yl)-9H-carbazole-3-carbaldehyde (6) were isolated for the first time from this plant. These compounds were screened for cytotoxicity in human cervical cancer (Hela), leukemia (K562), lung cancer (A549), non-small lung carcinoma (H1299) and liver cancer (SMMC-7721). Within the series of cytotoxic tests, compounds 4-6 displayed potent cytotoxic activity against H1299 and SMMC-7721, with the IC50 values of 6.19 to 26.84 µg/mL.


Asunto(s)
Aldehídos/farmacología , Antineoplásicos Fitogénicos/farmacología , Carbazoles/farmacología , Clausena/química , Compuestos Heterocíclicos con 3 Anillos/farmacología , Extractos Vegetales/farmacología , Tallos de la Planta/química , Aldehídos/aislamiento & purificación , Antineoplásicos Fitogénicos/aislamiento & purificación , Carbazoles/aislamiento & purificación , Doxorrubicina/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Células HeLa , Compuestos Heterocíclicos con 3 Anillos/aislamiento & purificación , Humanos , Concentración 50 Inhibidora , Células K562 , Extractos Vegetales/aislamiento & purificación
15.
Mutat Res ; 755(1): 68-72, 2013 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-23743014

RESUMEN

In November 1992, a radiation accident occurred in Xinzhou, due to the collection by a farmer of an unused (60)Co source; 37 individuals were exposed to ionizing radiation. Three individuals died and the farmer's 19-weeks-pregnant wife suffered acute radiation symptoms. Conventional chromosome analysis, cytokinesis-block micronuclei (CBMN) assay and fluorescence in situ hybridization (FISH) painting with three pairs of whole chromosome probes were used to analyze chromosomal aberrations for the pregnant female and her baby during the 16 years following the accident. The yields of dicentrics and rings (dic+r) continually declined between 41 days and 16 years after the accident. The frequency of binucleated MN also decreased over time for both mother and daughter. Sixteen years after exposure, the yields of dic+r and binucleated MN decreased to normal levels, but the reciprocal translocation frequencies remained elevated, for both mother and daughter. FISH results showed a decreasing yield of translocations with time. Based on the changes in maternal translocation frequency, the daughter's dose at the time of exposure was estimated as 1.82 (1.35-2.54)Gy. This was consistent with the clinical manifestations of severe mental retardation and low IQ score. FISH-based translocation analysis can be used for follow-up studies on accidental exposure and, after correction, for retrospective dose estimation for individuals prenatally exposed to radiation.


Asunto(s)
Aberraciones Cromosómicas/efectos de la radiación , Exposición a Riesgos Ambientales/efectos adversos , Feto/efectos de la radiación , Efectos Tardíos de la Exposición Prenatal/diagnóstico , Traumatismos por Radiación/diagnóstico , Adolescente , Adulto , China , Femenino , Estudios de Seguimiento , Humanos , Hibridación Fluorescente in Situ , Pruebas de Micronúcleos , Embarazo , Efectos Tardíos de la Exposición Prenatal/etiología , Dosis de Radiación , Traumatismos por Radiación/etiología , Liberación de Radiactividad Peligrosa , Sobrevivientes
16.
Biomed Environ Sci ; 25(5): 533-41, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23122310

RESUMEN

OBJECTIVE: We identify ionizing radiation-induced mitochondrial DNA (mtDNA) deletions in human lymphocytes and their distribution in normal populations. METHODS: Long-range polymerase chain reactions (PCR) using two pairs of primers specific for the human mitochondrial genome were used to analyze the lymphoblastoid cell line following exposure to 10 Gy (60)Co γ-rays. Limited-condition PCR, cloning and sequencing techniques were applied to verify the mtDNA deletions detected with long-range PCR. Human peripheral blood samples were irradiated with 0, 2 and 6 Gy (60)Co γ-rays, and real-time PCR analysis was performed to validate the mtDNA deletions. In order to know the distribution of mtDNA deletions in normal population, 222 healthy Chinese adults were also investigated. RESULTS: Two mtDNA deletions, a 7455-bp deletion (nt475-nt7929 in heavy strand) and a 9225-bp deletion (nt7714 -nt369 in heavy strand), occurring between two 8-bp direct repeats, were identified in lymphoblastoid cells using long-range PCR, limited-condition PCR and sequencing. These results were also observed for (60)Co γ-rays irradiated human peripheral blood cells. CONCLUSION: Two novel mtDNA deletions, a 7455-bp deletion and a 9225-bp deletion, were induced by ionizing radiation. The rate of the mtDNA deletions within a normal population was related to the donors' age, but was independent of gender.


Asunto(s)
Daño del ADN/efectos de la radiación , ADN Mitocondrial/genética , ADN Mitocondrial/efectos de la radiación , Eliminación de Gen , Linfocitos/efectos de la radiación , Radiación Ionizante , Línea Celular , Clonación Molecular , Radioisótopos de Cobalto , Daño del ADN/genética , Marcadores Genéticos , Humanos , Reacción en Cadena en Tiempo Real de la Polimerasa
17.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 22(3): 254-7, 2005 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15952108

RESUMEN

OBJECTIVE: To detect the characteristic chromosomal changes in Chinese children with infantile autism. METHODS: Chromosome aberrations in 68 cases of infantile autism were analyzed by high-resolution G-banding and fluorescence in situ hybridization (FISH) with bacterial artificial chromosome (BAC) clones. RESULTS: Chromosomal changes were detected in 4 cases by high-resolution G-banding: one case with t(4;6)(q23-24;p21), one case with longer p arm of chromosome 21 (21p+), and two cases with pericentric inversion of chromosome 9 (inv(9)) which was confirmed by C-banding. BAC FISH analysis was performed to confirm these observations and changes in chromosomes 2, 7 and 15, which are often found in autistic children. There could exist the translocation of t(4;6) (q25-26;p21.1). Chromosome changes often reported previously in chromosomes 2, 7 and 15 were not detected in this study. Inv(9) and 21p+ were not confirmed with present BAC clones. CONCLUSION: Chromosomal changes were detected in four cases of infantile autism, with a detectability of 5.9% , far lower than that (10% to 48%) reported in literature. The breakpoint of translocation could be detected more accurately using BAC FISH method.


Asunto(s)
Trastorno Autístico/genética , Aberraciones Cromosómicas , Hibridación Fluorescente in Situ/métodos , Trastorno Autístico/diagnóstico , Niño , Bandeo Cromosómico , Cromosomas Artificiales Bacterianos/genética , Femenino , Humanos , Masculino , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
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