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1.
Science ; 153(3737): 763-5, 1966 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-5940895

RESUMEN

Both actinomycin D and puromycin suppress the formation of colonies by cultured human kidney epithelial cells (T-l), but inactivation by puromycin is partially reversed with thyroid hormones. Uptake by the cells of L-thyroxine labeled with iodine-125, 60 to 80 percent of which is nuclear, is depressed by actinomycin and enhanced by puromycin. Genome and possibly nuclear membrane are implicated as initiating loci.


Asunto(s)
Epitelio/efectos de los fármacos , Riñón , Puromicina/farmacología , Tiroxina/farmacología , Triyodotironina/farmacología , Autorradiografía , Técnicas de Cultivo , ADN , Humanos , Isótopos de Yodo , ARN Mensajero
2.
Science ; 172(3985): 868-70, 1971 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-5572911

RESUMEN

Six subjects reported multiple starlike flashes and short streaks on exposure to neutrons of energies up to 25 million electron volts. The probable mechanism is interaction with the retinal rods by proton recoils and by alpha particles released from neutron reactions with carbon and oxygen. These observations are similar to light flashes and streaks seen by astronauts who are exposed to high-energy cosmic rays on translunar flight.


Asunto(s)
Neutrones , Percepción Visual , Partículas alfa , Humanos , Células Fotorreceptoras/fisiología
3.
Science ; 182(4111): 474-6, 1973 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-4744176

RESUMEN

Energetic heavy particles from an accelerator mnay be used to produce radiographs with high contrast and high depth resolution. Small differences in the stopping power of objects can be detected and permnanently recorded by using stacks of plastic track detectors. This method should aid in the diagnosis of soft-tissue abnormalities, including some tumnors, and make possible quantitative reconstruction of the internal density structure of objects.


Asunto(s)
Neoplasias/diagnóstico por imagen , Radiografía , Animales , Neoplasias Óseas/diagnóstico por imagen , Huesos/diagnóstico por imagen , Embrión de Pollo , Peces , Métodos , Isótopos de Oxígeno
4.
Science ; 174(4014): 1131-4, 1971 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-5133730

RESUMEN

Studies of the depth-ionization properties and the biological effects of heavy ion beams produced at the bevatron have extended work previously done with less energetic beams from other sources. Results indicate that heavy ion beams are suitable for tumor therapy, studies relating to space biology, and fundamental radiobiology.


Asunto(s)
Física Nuclear , Radiobiología , Nitrógeno , Dosis de Radiación , Radioisótopos , Radioterapia , Dosificación Radioterapéutica
5.
Clin Cancer Res ; 4(3): 697-711, 1998 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-9533540

RESUMEN

Although the antiestrogen tamoxifen has been the mainstay of therapy for estrogen receptor (ER)-positive breast cancer, successful treatment of responsive tumors is often followed by the acquisition of tamoxifen resistance. Subsequently, only 30-40% of patients have a positive response to second hormonal therapies. This lack of response might be explained by mechanisms for tamoxifen resistance that sensitize ER pathways to small amounts of estrogenic activity present in tamoxifen or that bypass ER pathways completely. To elucidate one possible mechanism of tamoxifen resistance, we treated ovariectomized tumor-bearing mice injected with fibroblast growth factor (FGF)-transfected MCF-7 breast carcinoma cells with the steroidal antiestrogen ICI 182,780 or one of two aromatase inhibitors, 4-OHA or letrozole. These treatments did not slow estrogen-independent growth or prevent metastasis of tumors produced by FGF-transfected MCF-7 cells in ovariectomized nude mice. FGF-transfected cells had diminished responses to ICI 182,780 in vitro, suggesting that autocrine activity of the transfected FGF may be replacing estrogen as a mitogenic stimulus for tumor growth. ER levels in FGF transfectants were not down-regulated, and basal levels of transcripts for estrogen-induced genes or of ER-mediated transcription of estrogen response element (ERE) luciferase reporter constructs in the FGF expressing cells were not higher than parental cells, implying that altered hormonal responses are not due to down-regulation of ER or to FGF-mediated activation of ER. These studies indicate that estrogen independence may be achieved through FGF signaling pathways independent of ER pathways. If so, therapies directed at the operative mechanism might produce a therapeutic response or allow a response to a second course of antiestrogen treatment.


Asunto(s)
Antineoplásicos/uso terapéutico , Inhibidores de la Aromatasa , Neoplasias de la Mama/tratamiento farmacológico , Resistencia a Antineoplásicos , Estradiol/análogos & derivados , Factores de Crecimiento de Fibroblastos/fisiología , Tamoxifeno/uso terapéutico , Androstenodiona/análogos & derivados , Androstenodiona/uso terapéutico , Androstenodiona/toxicidad , Animales , Antineoplásicos/toxicidad , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , División Celular/efectos de los fármacos , Línea Celular , Cloranfenicol O-Acetiltransferasa/biosíntesis , Inhibidores Enzimáticos/uso terapéutico , Inhibidores Enzimáticos/toxicidad , Estradiol/uso terapéutico , Estradiol/toxicidad , Antagonistas de Estrógenos/uso terapéutico , Antagonistas de Estrógenos/toxicidad , Femenino , Factores de Crecimiento de Fibroblastos/biosíntesis , Fulvestrant , Humanos , Letrozol , Luciferasas/biosíntesis , Ratones , Ratones Desnudos , Nitrilos/uso terapéutico , Nitrilos/toxicidad , Ovariectomía , Reacción en Cadena de la Polimerasa , ARN Mensajero/biosíntesis , Receptores de Progesterona/biosíntesis , Proteínas Recombinantes de Fusión/biosíntesis , Tamoxifeno/toxicidad , Transcripción Genética , Transfección , Trasplante Heterólogo , Triazoles/uso terapéutico , Triazoles/toxicidad , Células Tumorales Cultivadas
6.
Int J Radiat Oncol Biol Phys ; 8(12): 2109-20, 1982 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-6819271

RESUMEN

Quantitative studies at the BEVALAC have demonstrated some of the physical and radiobiological factors that promise to make accelerated heavy ions important for the therapy of cancer. The measured physical dose-biological effect relationships allow the safe and effective delivery of therapeutic schedules of heavy ions. Among the charged particle beams available, carbon, neon and helium ions in the "extended Bragg peak mode" have optimal physical and biological effectiveness for delivery of therapy to deep seated tumors. The depth-dose profiles of these beams protect intervening and adjacent tissues as well as tissues beyond the range of the particles. For the treatment of hypoxic tumors, silicon and argon beams are being considered because they significantly depress the radiobiological oxygen effect in the region of the extended Bragg ionization peak. The depth-effectiveness of the argon beam is somewhat limited, however, because of primary particle fragmentation. Silicon beams have a depth-dose profile which is intermediate between that of neon and argon, and are candidates to become the particle of choice for maximizing high LET particle effects. Heavy accelerated ions depress enzymatic repair mechanisms, decrease variations of radiosensitivity during the cell division cycle, cause greater than expected delays in cell division, and decrease the protective effects of neighboring cells in organized systems. Near the Bragg peak, enhancement of heavy particle effects are observed in split dose schedules. Late and carcinogenic effects are being studied. With the newly developed Repair-Misrepair theory we can quantitatively model most observations.


Asunto(s)
Partículas Elementales , Animales , Supervivencia Celular/efectos de la radiación , Reparación del ADN/efectos de la radiación , Relación Dosis-Respuesta en la Radiación , Humanos , Neoplasias Experimentales/radioterapia , Oxígeno/fisiología , Radioterapia de Alta Energía , Ratas , Efectividad Biológica Relativa , Rabdomiosarcoma/radioterapia
7.
Int J Radiat Oncol Biol Phys ; 8(12): 2191-8, 1982 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-6819279

RESUMEN

A clinical radiotherapeutic trial using heavy charged particles in the treatment of human cancers has accrued over 400 patients since 1975, 378 of whom were treated with particles and 28 with low LET photons as control patients. Heavy charged particle radiotherapy offers the potential advantages of improved dose localization and/or enhanced biologic effect, depending on particle selected for treatment. Target sites have included selected head and neck tumors, ocular melanomata, malignant gliomata of the brain, carcinoma of the esophagus, carcinoma of the stomach, carcinoma of the pancreas, selected juxtaspinal tumors and other locally advanced, unresectable tumors. A Phase III prospective clinical trial has been started in carcinoma of the pancreas using helium ions. Phase I-II studies are underway with heavier particles such as carbon, neon and argon ions in order to prepare for prospective Phase III trials. Silicon ions are also under consideration for clinical trial. These studies are supported by the United States Department of Energy and National Institutes of Health.


Asunto(s)
Partículas Elementales , Neoplasias/radioterapia , Radioterapia de Alta Energía , Adulto , Anciano , Carcinoma de Células Escamosas/radioterapia , Ensayos Clínicos como Asunto , Neoplasias Esofágicas/radioterapia , Neoplasias del Ojo/radioterapia , Femenino , Helio , Humanos , Iones , Masculino , Melanoma/radioterapia , Persona de Mediana Edad , Neoplasias Pancreáticas/radioterapia , Radioterapia de Alta Energía/efectos adversos , Neoplasias Craneales/radioterapia , Neoplasias de la Columna Vertebral/radioterapia
8.
Biotechniques ; 29(4): 884-90, 2000 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11056820

RESUMEN

Recombinant retroviruses are a common vehicle to deliver an exogenous gene to a target cell, which makes them a useful tool in the field of gene therapy. A major drawback to using recombinant retroviruses is the low titer achieved, resulting in a limited number of target cells infected and subsequently poor expression of a transgene. In this study, we created an ecotropic producer cell line that contained recombinant mouse nerve growth factor (NGF) and the reporter gene LacZ. This cell line, termed psi 2/LIG/NGF, was treated with the drug trichostatin A, an inhibitor of histone deacetylase. At a concentration of 3 microM trichostatin A, the retroviral titer of this producer cell line was increased 34-fold relative to untreated control cells and 3.4-fold compared to the commonly used hyperacetylating compound sodium butyrate. Producer cells treated with trichostatin A also increased the number of primary rat marrow stromal cells infected 5.8-fold compared to untreated producer cells. These results offer a simple and effective solution for converting low titer producer cell clones to higher titer clones, which can be easily tested and applied.


Asunto(s)
Inhibidores Enzimáticos/farmacología , Terapia Genética , Inhibidores de Histona Desacetilasas , Ácidos Hidroxámicos/farmacología , Retroviridae/efectos de los fármacos , Células 3T3 , Animales , Butiratos/farmacología , Relación Dosis-Respuesta a Droga , Ratones , Factor de Crecimiento Nervioso/farmacología , Retroviridae/genética
9.
Hum Pathol ; 15(1): 48-54, 1984 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-6363273

RESUMEN

Since 1958, 781 patients at Lawrence Berkeley Laboratory have received helium-particle stereotactic radiosurgery to the adenohypophysis. Autopsy findings in 15 of these patients are reported. Ten patients received pituitary radiation (average dose, 116 Gy in six fractions) for progressive neovascularization retinopathy due to diabetes mellitus. Evidence of a time-dependent course of progressive fibrosis in their pituitary glands was found. Five patients were treated for eosinophilic adenomas. Although they had lower average doses of radiation (56 Gy in six fractions), their pituitary glands showed cystic cavitation of the adenomas. The adenomas thus appeared more radiosensitive than the normal pars anterior, which, in turn, was more radiosensitive than the adjacent neurohypophysis. No significant radiation changes were found in the surrounding brain or cranial nerves. The endocrine organs under pituitary control showed varying degrees of atrophy, and clinical tests revealed progressive hypofunction. It was concluded that charged-particle therapy produced a sharply delineated focal radiation lesion confined to the pituitary gland but did not cause injury to the critical structures of the surrounding central nervous system.


Asunto(s)
Encéfalo/efectos de la radiación , Glándulas Endocrinas/efectos de la radiación , Hipófisis/efectos de la radiación , Irradiación Hipofisaria , Acromegalia/radioterapia , Adulto , Anciano , Neoplasias de la Mama/radioterapia , Retinopatía Diabética/radioterapia , Relación Dosis-Respuesta en la Radiación , Femenino , Humanos , Técnicas para Inmunoenzimas , Persona de Mediana Edad , Tirotropina/análisis , Factores de Tiempo
10.
Invest Radiol ; 13(2): 163-70, 1978.
Artículo en Inglés | MEDLINE | ID: mdl-207658

RESUMEN

Heavy-ion radiography is performed by the passage of a beam of nuclei accelerated to energies of several hundred MeV/nucleon through an object. The technique of recording transmitted nuclei in a downstream stack of plastic sheets affords excellent resolution of density by recording the nuclei only at their stopping points. Imaging of a phantom--which stimulated tumors of low density contrast in a body part--by conventional radiography, computed tomographic scanning and the heavy-ion technique indicated superior density resolution for heavy-ion imaging at radiation dose. Superior imaging of tumors in pathologic specimens was demonstrated for heavy-ion imaging compared to conventional radiography. Values of stopping power for various tumors and normal tissues were determined by a computer-aided technique. Heavy-ion radiography shows promise for superior imaging of low contrast tumors at relatively low radiation low levels.


Asunto(s)
Neoplasias/diagnóstico , Aceleradores de Partículas , Tendón Calcáneo , Adenocarcinoma/diagnóstico , Neoplasias Encefálicas/diagnóstico , Neoplasias de la Mama/diagnóstico , Carbono , Carcinoma Intraductal no Infiltrante/diagnóstico , Carcinoma de Células Pequeñas/diagnóstico , Femenino , Pie , Humanos , Iones , Neoplasias Hepáticas/diagnóstico , Melanoma/diagnóstico , Modelos Estructurales , Metástasis de la Neoplasia , Oxígeno , Tendones
11.
J Neurotrauma ; 18(3): 287-301, 2001 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11284549

RESUMEN

Grafting of genetically modified cells that express therapeutic products is a promising strategy in spinal cord repair. We have previously grafted BDNF-producing fibroblasts (FB/BDNF) into injured spinal cord of adult rats, but survival of these cells requires a strict protocol of immune suppression with cyclosporin A (CsA). To develop a transplantation strategy without the detrimental effects of CsA, we studied the properties of FB/BDNF that were encapsulated in alginate-poly-L-ornithine, which possesses a semipermeable membrane that allows production and diffusion of a therapeutic product while protecting the cells from the host immune system. Our results show that encapsulated FB/BDNF, placed in culture, can survive, secrete bioactive BDNF and continue to grow for at least one month. Furthermore, encapsulated cells that have been stored in liquid nitrogen retain the ability to grow and express the transgene. Encapsulated FB/BDNF survive for at least one month after grafting into an adult rat cervical spinal cord injury site in the absence of immune suppression. Transgene expression decreased within two weeks after grafting but resumed when the cells were harvested and re-cultured, suggesting that soluble factors originating from the host immune response may contribute to the downregulation. In the presence of capsules that contained FB/BDNF, but not cell-free control capsules, there were many axons and dendrites at the grafting site. We conclude that alginate encapsulation of genetically modified cells may be an effective strategy for delivery of therapeutic products to the injured spinal cord and may provide a permissive environment for host axon growth in the absence of immune suppression.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/uso terapéutico , Fibroblastos/trasplante , Expresión Génica/efectos de los fármacos , Supervivencia de Injerto/inmunología , Traumatismos de la Médula Espinal/tratamiento farmacológico , Alginatos/uso terapéutico , Animales , Materiales Biocompatibles/uso terapéutico , Factor Neurotrófico Derivado del Encéfalo/inmunología , Cápsulas , Embrión de Pollo , Femenino , Fibroblastos/inmunología , Expresión Génica/fisiología , Genes Reporteros/efectos de los fármacos , Genes Reporteros/fisiología , Ácido Glucurónico , Ácidos Hexurónicos , Péptidos/inmunología , Péptidos/uso terapéutico , Ratas , Ratas Sprague-Dawley , Traumatismos de la Médula Espinal/inmunología , Tensoactivos/uso terapéutico
12.
Radiat Res ; 103(1): 1-33, 1985 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-3906741

RESUMEN

Interplanetary space contains fluxes of fast moving atomic nuclei. The distribution of these reflects the atomic composition of the universe, and such particles may pose limitations for space flight and for life in space. Over the past 50 years, since the invention of Ernest Lawrence's cyclotron, advances in accelerator technology have permitted the acceleration of charged nuclei to very high velocities. Currently, beams of any stable isotope species up to uranium are available at kinetic energies of several hundred MeV/nucleon at the Berkeley Bevalac. Recently, new areas of particle physics research relating to the mechanisms of spallation and fission have opened up for investigation, and it is now realistic to search for nuclear super-dense states that might be produced in heavy nuclear collisions. The heavy ions hold interest for a broad spectrum of research because of their effectiveness in producing a series of major lesions in DNA along single particle tracks and because of the Bragg depth ionization properties that allow the precise deposition of highly localized doses deep in the human body. Individual heavy ions can also interrupt the continuity of membraneous regions in cells. Heavy ions, when compared to low-LET radiation, have increased effectiveness for mammalian cell lethality, chromosome mutations, and cell transformation. The molecular mechanisms are not completely understood but appear to involve fragmentation and reintegration of DNA. Cells attempt to repair these lesions, and many of the deleterious effects are due to misrepair or misrejoining of DNA. Heavy ions do not require the presence of oxygen for producing their effects, and hypoxic cells in necrotic regions have nearly the same sensitivity as cells in well-oxygenated tissues. Heavy ions are effective in delaying or blocking the cell division process. Heavy ions are also strong enhancers of viral-induced cell transformation, a process that requires integration of foreign DNA. Some cell lines, known to be radioresistant to X rays, have exhibited greater sensitivity to heavy ions. These radiobiological properties, combined with the ability to deliver highly localized internal doses, make accelerated heavy ions potentially important radiotherapeutic tools. Other novel approaches include the utilization of radioactive heavy beams as instant tracers. Heavy-ion radiography and microscopy respond to delicate changes in tissue electron density. Dose localization with helium ions has achieved excellent results for pituitary tumors, tumors adjacent to the spinal cord, and ocular melanomas. We are working on adapting silicon- and neon-ion beams for controlled therapy studies.(ABSTRACT TRUNCATED AT 400 WORDS)


Asunto(s)
Iones , Radiobiología , Acromegalia/radioterapia , Animales , Argón , Transformación Celular Viral/efectos de la radiación , Córnea/efectos de la radiación , ADN/efectos de la radiación , Reparación del ADN , Relación Dosis-Respuesta en la Radiación , Transferencia de Energía , Hormona del Crecimiento/sangre , Helio , Humanos , Mamografía , Microscopía/métodos , Microscopía Electrónica de Rastreo , Aceleradores de Partículas , Fenómenos Físicos , Física , Neoplasias Hipofisarias/radioterapia , Plantas/genética , Plantas/ultraestructura , Ratas , Efectividad Biológica Relativa , Uranio
13.
Radiat Res ; 114(2): 281-96, 1988 May.
Artículo en Inglés | MEDLINE | ID: mdl-3375428

RESUMEN

A temperature-sensitive mutant for protein synthesis, CHO-tsH1, has been compared to the wild-type (WT) cell, CHO-SC1, in single- and split-radiation-dose schemes. When the exponentially growing mutant and the wild-type cells were treated at 40 degrees C for up to 3 h prior to split doses of X rays, survival was progressively reduced in the mutant compared to the wild type. In addition, if a 2-h split-dose scheme was used with a treatment of 40 degrees C given before the first dose, between the dose fractions and after the second dose, the recovery from sublethal damage (SLD) was almost completely inhibited in the mutant cells. These observations implied that a pool of proteins was involved in the recovery from sublethal X-ray damage. However, if molecular repair was measured in the mutant cell by the alkaline-unwinding technique under the same time and temperature schemes as those demonstrating a reduction in the recovery from SLD, no difference in the kinetics of DNA strand rejoining was observed compared to similar measurements made under conditions permitting SLD recovery. Misrepair processes may permit restoration of DNA strand integrity but not allow functional repair. Split-dose experiments were also done using cycloheximide to chemically inhibit protein synthesis. Under conditions which mimicked those used in the temperature-shift experiments both cell lines showed a reduction in the recovery from sublethal damage comparable in magnitude to that observed in the mutant cells when they were treated with 40 degrees C. Both the chemical and thermal inhibition of protein synthesis substantiate its necessity for the recovery from sublethal damage.


Asunto(s)
Reparación del ADN , Biosíntesis de Proteínas , Animales , Línea Celular , Supervivencia Celular/efectos de la radiación , Cricetinae , Cricetulus , Mutación , Dosis de Radiación , Temperatura
14.
Radiat Res ; 129(3): 272-80, 1992 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-1542716

RESUMEN

The combined effects of heavy-ion radiation and hyperthermia on the survival of CHO-SC1 cells and its temperature-sensitive (ts) mutant tsH1 cells were studied using accelerated neon ions followed by mild heating at 41.5 degrees C. The sequence of application of heat and high-LET radiation is significant to cell-killing effects. Heat applied to cells prior to irradiation with neon plateau ions (LET = 32 keV/microns) was less effective than heat applied immediately after irradiation. The ability of cells to synthesize new proteins plays a key role in this sequence-dependent thermal sensitization. When protein synthesis was shut down in tsH1 cells, the thermal enhancement of cell killing by high-LET radiation was the same regardless of the sequence. The thermal enhancement of radiation-induced cell killing was LET-dependent for the SC1 cells, but this was not clearly demonstrated in the tsH1 cells. Furthermore, the RBE of heated SC1 cells varied with LET and reached a maximum of greater than 3 at 80 keV/microns. In the absence of protein synthesis, the maximum RBE value was reduced to 2.6. These results suggest that the accumulation of cellular damage caused by exposure to densely ionizing particles with increasing LETs can be potentiated with active protein synthesis during postirradiation heat treatment.


Asunto(s)
Supervivencia Celular/efectos de la radiación , Calor , Biosíntesis de Proteínas , Animales , Células CHO , Cricetinae , Transferencia de Energía , Efectividad Biológica Relativa
15.
Radiat Res ; 138(3): 343-51, 1994 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-8184008

RESUMEN

Chromosomal fragmentation was examined in G1-phase Chinese hamster ovary cells using the premature chromosome condensation (PCC) technique. The yield and distribution of chromatin breaks, the lesions revealed by PCC, were measured in cells exposed to X rays or each of nine particle beams covering a range of LET from 0.56 to 2700 keV/microns. The average number of breaks per cell was found to be linearly proportional to the fluence of high-LET neon ions (183 keV/microns). Assuming a linear response for the other beams, the level of breakage per unit dose rose from a plateau at the lowest LET values to a peak in the 100-200 keV/microns range and then declined continuously thereafter, eventually falling well below the low-LET plateau. The maximum breakage RBE was 1.5. The average number of breaks per particle traversal rose steadily from 0.006 to 11 breaks/cell as the LET increased from 0.56 to 2700 keV/microns. The breaks were distributed randomly within the cell population after low-LET irradiation, but became progressively over-dispersed with increasing LET. Rejoining of prematurely condensed chromosomes plus fragments was followed for up to 5 h for four particle beams having LET values between 0.56 and 183 keV/microns. An LET-dependent trend toward higher levels of residual fragments was observed.


Asunto(s)
Cromosomas/efectos de la radiación , Daño del ADN , Reparación del ADN , Animales , Células CHO , Cromatina/efectos de la radiación , Cricetinae , Relación Dosis-Respuesta a Droga , Transferencia de Energía , Mitosis , Rayos X
16.
Radiat Res ; 104(2 Pt 1): 200-13, 1985 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-3001817

RESUMEN

The enhancement effects of ionizing and ultraviolet radiation on the efficiency of DNA-mediated gene transfer were studied. The established cell line, Rat-2, consists of cells that are density-dependent contact-inhibited and produce flat monolayers in vitro. When these cells are infected with SV40 virus, a small fraction of cells becomes morphologically "transformed" due to the stable expression of the viral A-gene. Rat-2 cells are competent for DNA-mediated gene transfer, deficient in thymidine kinase activity (TK-), and will die in HAT selective media. Confluent Rat-2 cells were transfected with purified SV40 viral DNA (via calcium phosphate precipitation), irradiated with either X rays or ultraviolet, trypsinized, plated, and assayed for the formation of foci on Rat-2 monolayers. Both ionizing and ultraviolet radiation enhanced the frequency of A-gene transformants/survivor compared to unirradiated transfected cells. These enhancements were nonlinear and dose dependent. A recombinant plasmid, pOT-TK5, was constructed that contained the SV40 virus A-gene and the Herpes Simplex virus (HSV) thymidine kinase (TK) gene. Confluent Rat-2 cells transfected with pOT-TK5 DNA and then immediately irradiated with either X rays or 330 MeV/amu argon particles at the Berkeley BEVALAC showed a higher frequency of HAT+ colonies/survivor than unirradiated transfected cells. In both cases the enhancement contained a linear and a higher order component in dose, but the argon ions were at least twice more efficient than X rays in producing enhancement per unit dose. Rat-2 cells transfected with pOT-TK5, X-irradiated, and assayed for either TK transformation or A-gene transformation showed the same dose dependence for radiation enhancement. Rat-2 cells transfected with the plasmid, pTK2, containing only the HSV TK-gene were enhanced for TK transformation by both X rays and ultraviolet radiation. SV40 A-gene products are not necessary for the radiation enhancement of the efficiency of gene transfer. This in vitro system will be used to study the lesions produced by ionizing radiation on mammalian cell DNA that may act as substrates for integration of exogenously introduced plasmid DNA.


Asunto(s)
Virus 40 de los Simios/genética , Transfección/efectos de la radiación , Animales , Línea Celular , Plásmidos , Genética de Radiación , Radiación Ionizante , Ratas , Timidina Quinasa/genética , Transformación Genética/efectos de la radiación , Rayos Ultravioleta
17.
Radiat Res ; 115(1): 54-69, 1988 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-3393635

RESUMEN

The synergistic effects of low- and high-LET radiations were further studied with partially synchronized Chinese hamster V79 cells. Principally, nearly monoenergetic 425 MeV/u neon ions and 570 MeV/u argon ions produced near the Bragg peak were employed as the high-LET radiations and 225 kVp X rays as the low-LET counterpart. It was found that the killing effect due to damage interaction after sequential irradiations with the particle beam and X rays varies throughout the cell cycle. The greatest effect was observed in late-S phase which was most resistant to either of the radiations. The effect was quantitatively less in the G1/S border and in G2. Effects on pure mitotic cells have not been investigated in this study. For all cell stages studied, a dose of high-LET particles modified the shape of the X-ray survival curve in a way similar to the modification predicted by an appropriately selected X-ray dose. This finding suggests that the mechanism for the synergistic effects is similar to that operating for sequential treatments with X rays alone. Experiments with an S population, either incubated at 37 degrees C or room temperature between fractionation of high- and low-LET radiation treatments further verified that the damage involved is a repairable type. At a certain fractionation interval (6 to 8 h) following a dose of high-LET treatment, initially asynchronous cells were found to be very sensitive to X-irradiation. It is noteworthy that the net killing measured at this "radiosensitive window" was as effective as the killing observed by "immediately" sequential treatments with the same doses of high- and low-LET radiations. Such a time window also existed when the order of the treatment sequence was reversed except that the time of occurrence was earlier and the window was broader. This sensitization effect may be explained by radiation-induced G2 arrest together with an increase of radiosensitivity as the previously irradiated cells progress into S phase. Radiotherapy strategies using combined high-LET and low-LET radiations for rapidly proliferative tumors are presented.


Asunto(s)
Ciclo Celular/efectos de la radiación , Supervivencia Celular/efectos de la radiación , Animales , Argón , Línea Celular/efectos de la radiación , Transferencia de Energía , Interfase , Neón , Dosis de Radiación , Rayos X
18.
Brain Res ; 204(2): 436-40, 1981 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-6257329

RESUMEN

The change in excitability of unstained nerve cells from neonatal rat cerebellum was measured as a function of the energy flux and wavelength of incident laser light. The energy flux was in the range of 0 to 100 microJ/sq. microns. 6 wavelengths between 490 and 685 nm were used. Laser pulses above a threshold energy flux significantly reduced the cells' excitability as measured by extracellular stimulation. The sensitivity of the cells, defined as the inverse of the threshold energy density, increased by an order of magnitude toward the shorter wavelengths. These results are consistent with primary absorption of the light by mitochondrial enzymes, resulting in local heating followed by mitochondrial calcium release into the cytoplasm.


Asunto(s)
Cerebelo/fisiología , Rayos Láser , Transmisión Sináptica , Animales , Técnicas de Cultivo , Potenciales Evocados , Neuronas/fisiología , Ratas
19.
Brain Res ; 874(2): 87-106, 2000 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-10960593

RESUMEN

Recent advances in the isolation and characterization of neural precursor cells suggest that they have properties that would make them useful transplants for the treatment of central nervous system disorders. We demonstrate here that spinal cord cells isolated from embryonic day 14 Sprague-Dawley and Fischer 344 rats possess characteristics of precursor cells. They proliferate as undifferentiated neurospheres in the presence of EGF and bFGF and can be maintained in vitro or frozen, expanded and induced to differentiate into both neurons and glia. Exposure of these cells to serum in the absence of EGF and bFGF promotes differentiation into astrocytes; treatment with retinoic acid promotes differentiation into neurons. Spinal cord cells labeled with a nuclear dye or a recombinant adenovirus vector carrying the lacZ gene survive grafting into the injured spinal cord of immunosuppressed Sprague-Dawley rats and non-immunosuppressed Fischer 344 rats for up to 4 months following transplantation. In the presence of exogenously supplied BDNF, the grafted cells differentiate into both neurons and glia. These spinal cord cell grafts are permissive for growth by several populations of host axons, especially when combined with exogenous BDNF administration, as demonstrated by penetration into the graft of axons immunopositive for 5-HT and CGRP. Thus, precursor cells isolated from the embryonic spinal cord of rats, expanded in culture and genetically modified, are a promising type of transplant for repair of the injured spinal cord.


Asunto(s)
Trasplante de Tejido Fetal , Neuronas/citología , Neuronas/trasplante , Esferoides Celulares/trasplante , Médula Espinal/embriología , Médula Espinal/cirugía , Animales , Axones/fisiología , Bovinos/sangre , Bovinos/embriología , Diferenciación Celular/fisiología , Separación Celular , Supervivencia Celular/fisiología , Sangre Fetal/fisiología , Sustancias de Crecimiento/farmacología , Neuronas/fisiología , Fenotipo , Preservación Biológica , Ratas , Ratas Endogámicas F344 , Ratas Sprague-Dawley , Esferoides Celulares/fisiología , Médula Espinal/citología , Médula Espinal/efectos de los fármacos , Traumatismos de la Médula Espinal/cirugía , Factores de Tiempo , Tretinoina/farmacología
20.
Med Phys ; 17(2): 158-62, 1990.
Artículo en Inglés | MEDLINE | ID: mdl-2333041

RESUMEN

Accelerated heavy-ion beams used in biological and medical research are often utilized in conjunction with absorbers which lead to the fragmentation of the beam. The BERKLET, initially a two-stage solid-state telescope detector, was designed to make rapid, on-line energy and linear energy transfer (LET) measurements of individual particles in a heavy-ion beam, thus allowing characterization of fragmented beams. From data collected with the BERKLET, one is able to determine a number of important parameters. These include: residual energy and LET histograms for the full beam and for the individual Z components, relative number of particles with a given Z, and dose and track average LET's for the full beam and for the individual Z's. Improvements to the BERKLET design and changes in data analysis are discussed and contrasted with the results of an earlier BERKLET configuration. The most notable improvements are the addition of a thin scintillation detector for improved LET measurement, a tenfold improvement in the dynamic range of the event discriminator, reported here as 1:2000, and dual high-and low-gain amplification of the LET signals, permitting the identification of particles with Z's ranging from 12 down to 1.


Asunto(s)
Aceleradores de Partículas/instrumentación , Radiometría/instrumentación , Transferencia de Energía , Iones
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