RESUMEN
A new HPLC system coupled with multiple detectors - Diode array detector (DAD), fluorescence detector (FLD), electrochemical amperometric detector (ADC) and mass spectrometry detector (MSD) was developed for the characterization and differentiation of tannin-containing herbal drugs included in The European Pharmacopoeia. The HPLC separation system consisted of an Agilent ZORBAX Eclipse XDB C18 column and a gradient water and methanol as the mobile phase which was kept at a flow rate of 0.3 mL x min(-1). Four kinds of detectors were connected by a micro-splitter valve and simultaneously recorded the response of each analytical sample. Thirty-one samples from eight kinds of tannin-containing drugs were measured using this HPLC system and their signals from all detectors were comprehensively processed via principal component analysis (PCA). The statistic result demonstrates that thirty-one batches from different herbal drugs can be reasonably identified and systematically classified by their chemical fingerprints. The proposed multi-detector HPLC method aided by chemometrics not only offers a new pattern for the study of tannin-containing herbs, but also provides a useful foundation for quality control of herbal medicines.
Asunto(s)
Preparaciones de Plantas/análisis , Taninos/análisis , Cromatografía Líquida de Alta Presión/instrumentación , Cromatografía Líquida de Alta Presión/métodos , Electroquímica , Espectrometría de Masas , Plantas Medicinales/química , Análisis de Componente Principal , Estándares de Referencia , Reproducibilidad de los Resultados , Soluciones , Espectrometría de FluorescenciaRESUMEN
Newcastle Disease (ND) is a highly pathogenic disease of avian species which is caused by Newcastle Disease Virus (NDV). It is one of the major causes of mortality and morbidity to poultry industry in the third world countries. Currently, there is no treatment measures against ND; the only existing measure is vaccination, though it is incapable to offer 100% immunity. In Tanzania, the leaves of Synadenium glaucescens Pax. are traditionally used for treatment of various ailments including ND. Previously, its leaves extract has been scientifically confirmed to exhibit anti-NDV activity though bioactive compound(s) responsible for this activity is/are unknown. Therefore, this study was aimed to evaluate anti-NDV activity of 3ß-Friedelanol (1) and 3α-friedelanol (2) isolated from its leaves extract. Isolation of these compounds was achieved by column chromatography method whereas, their chemical structures were determined by Nuclear Magnetic Resonance (NMR) data and by comparing with the available literature NMR data. Anti-NDV activity study was done in embryonated chicken eggs (ECEs). Treatment of NDV inoculated ECEs with 3ß-Friedelanol (1) reduced the viral load to zero and maintained the survival of embryos, this was revealed by continuous organs formation and increase in embryo weights with no significant different (p > 0.05) from un-inoculated ECE. These effects suggest that, 3ß-Friedelanol (1) possesses anti-NDV activity. Therefore, existence of 3ß-Friedelanol (1) in the leaves of S. glaucescens may justify its earlier described anti-NDV activity and traditional use in the treatment of ND. Hence, its leaves extract may be considered for development of anti-NDV herbal formulation while 3ß-Friedelanol could either serve as a drug or lead compound for synthesis of anti-NDV drugs.
Asunto(s)
Enfermedad de Newcastle , Enfermedades de las Aves de Corral , Triterpenos , Animales , Pollos , Enfermedad de Newcastle/tratamiento farmacológico , Virus de la Enfermedad de Newcastle , Ácido Oleanólico/análogos & derivados , Extractos Vegetales/farmacologíaRESUMEN
A semisterile male translocation heterozygote [t(2; 14) 1Gso] that exhibited neurological symptoms and an inability to swim (diver) was found among the offspring of male mice treated with triethylenemelamine. All breeding and cytogenetic data showed a complete concordance between translocation heterozygosity and the neurological disorders. Homozygosity for the translocation seemed to be lethal at an early embryonic stage. Despite the distinctive neurologic symptoms, no anatomic or histological defects in either the ear or in the central nervous system were observed. Thus, a balanced chromosomal translocation can produce disease with an inheritance pattern that mimics a single dominant gene defect.
Asunto(s)
Ratones Mutantes Neurológicos/genética , Translocación Genética , Animales , Mapeo Cromosómico , Femenino , Heterocigoto , Humanos , Masculino , Ratones , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Distrofias Musculares/genética , Trietilenomelamina/farmacologíaRESUMEN
Local anaesthetics (LAs) are frequently used for diagnostic procedures in equine veterinary practice. The objective of this study was to investigate the physico-chemical stability and bacterial contamination of bupivacaine, lidocaine and mepivacaine used for lameness examinations in horses. The LAs were stored in 12 different groups at different temperatures (-18 °C to 70 °C), light intensities and in common veterinary field conditions for up to 16 months. The pH, presence of bacterial contamination and concentrations of LAs and methylparaben (a preservative present in lidocaine) were determined serially in both new and repeatedly punctured (RP) vials. Mepivacaine remained chemically stable. A 1.9% increase in bupivacaine concentration was evident in one group, whereas a 1.9-3.7% decrease was noted in six groups. Risk factors associated with a change in concentration were light and RP vials. Lidocaine concentration decreased 6.3% in one group and increased 5.3-7.2% in two groups. Risk factors for degradation were heat and RP vials whereas storage in practice vehicles was a risk factor for increased concentrations. Methylparaben decreased 8.3-75.0% in seven groups, and RP vials, heat and storage in practice vehicles were risk factors for degradation. No contamination was present in any of the LAs and pH remained stable. Commercially available solutions of lidocaine, mepivacaine and bupivacaine stored under common veterinary field conditions are extremely stable and sterile for extended periods. The minor changes in concentration documented in this study are unlikely to affect anaesthetic efficacy during equine lameness examinations. When using products containing methylparaben, degradation of the preservative over time is to be expected.
Asunto(s)
Anestésicos Locales/química , Bupivacaína/química , Contaminación de Medicamentos , Lidocaína/química , Mepivacaína/química , Animales , CaballosRESUMEN
The relative induction of dominant-lethal mutations and heritable translocations in triethylenemelamine-treated postmeiotic germ cells of mice was determined depending on the stage treated. Males were mated either 11.5-14.5 days after treatment (middle spermatids) or less than 2.5 hours after treatment (fully mature sperm). Results clearly showed that, even through similar levels of dominant-lethal mutations were induced in fully mature sperm and in middle spermatids, the frequency of heritable translocations induced in mature sperm was markedly lower than that induced in middle spermatids. This observation was used, together with earlier ones, to suggest a mechanism by which dominant-lethal mutations and heritable translocations are produced following chemical treatment of male postmeiotic germ cels.
Asunto(s)
Genes Dominantes/efectos de los fármacos , Genes Letales/efectos de los fármacos , Mutación , Espermátides/fisiología , Espermatozoides/fisiología , Translocación Genética/efectos de los fármacos , Trietilenomelamina/farmacología , Animales , Femenino , Fertilización , Tamaño de la Camada/efectos de los fármacos , Masculino , Ratones , Embarazo , Espermátides/efectos de los fármacos , Espermatozoides/efectos de los fármacosRESUMEN
1. The action of hexamethonium has been studied at a range of muscarinic receptors in vitro by use of both functional and radioligand binding studies. 2. In functional studies, hexamethonium exhibited little or no significant (P less than 0.05) antagonism of contractile responses to carbachol at muscarinic receptors in the guinea-pig ileum, oesophageal muscularis mucosae, urinary bladder and trachea. However, antagonism was observed at muscarinic receptors in the guinea-pig left atria mediating negative inotropic responses and the calculated pKB value was 3.80. Hexamethonium also antagonized contractile responses to carbachol in the canine saphenous vein. The pKB value at these receptors was 3.75. 3. In the presence of 3.2 mM hexamethonium, the pA2 value for methoctramine at atrial muscarinic receptors was reduced by approximately 10 fold (control pA2 value was 7.81 +/- 0.05; pA2 value in hexamethonium was 6.73 +/- 0.04). In contrast at tracheal muscarinic receptors, the pA2 values for methoctramine were unaffected in the presence of 3.2 mM hexamethonium (control pA2 = 5.58 +/- 0.07; pA2 value in hexamethonium was 5.63 +/- 0.12). All values quoted are mean +/- s.e. mean, n = 8. 4. In competition radioligand binding studies, hexamethonium exhibited a higher affinity for cardiac M2 receptors (pKi = 3.68) than for cerebrocortical M1 receptors (pKi = 3.28) or for submaxillary gland M3 receptors (pKi = 2.61). At M2 receptors hexamethonium at concentrations of 0.1-10 mM, increased the half life of the dissociation rate of [3H]-N-methylscopolamine 1.6-4.3 fold. This was observed at M3 receptors only at 10 mM, when the half life was increased 1.7 fold. 5. We conclude that hexamethonium, in addition to its well characterized nicotinic antagonist properties, can act as a weak muscarinic antagonist and differentiates between cardiac M2 receptors and glandular/smooth muscle M3 receptors. However, hexamethonium differentiates less clearly between M1 and M2 receptors. The selectivity between M2 and M3 receptors observed in the present study with hexamethonium is comparable to other M2 selective antagonists such as AF-DX 116 and himbacine. 6. Caution should be exercised with regard to the inclusion of hexamethonium in functionsal studies of M2 muscarinic receptor subtypes at concentrations of 0.1 mm and above.
Asunto(s)
Compuestos de Hexametonio/farmacología , Músculo Liso Vascular/efectos de los fármacos , Receptores Muscarínicos/efectos de los fármacos , Animales , Carbacol/farmacología , Diaminas/farmacología , Cobayas , Técnicas In Vitro , Cinética , Contracción Muscular/efectos de los fármacos , Miocardio/metabolismo , N-Metilescopolamina , Pirenzepina/farmacología , Cloruro de Potasio/farmacología , Derivados de Escopolamina/farmacología , Glándula Submandibular/efectos de los fármacos , Glándula Submandibular/metabolismoRESUMEN
The formation of three oxidant-derived products of 5-aminosalicylic acid (5-ASA) in vivo was demonstrated in patients with active ulcerative colitis as well as in healthy subjects. The products were isolated from faeces by preparative HPLC and their chemical structures were found to be oxidation products of 5-ASA using 1H-NMR spectroscopy and mass spectrometry. Reactions carried out in vitro between 5-ASA and oxidants suggested to be present in the inflamed bowel verified that the hypochlorite-mediated oxidation of 5-ASA as well as the haemoglobin-catalysed H2O2-dependent oxidation of 5-ASA resulted in the formation of a single oxidation product of 5-ASA. This product was similar to, but not identical to any of the products identified in faeces from patients receiving 5-ASA. Oxygen radical-mediated oxidation of 5-ASA gave several products, different from the products isolated. Finally, it was verified that the products formed in vivo are not formed as a result of autooxidation of 5-ASA either in faeces extract or in pharmaceuticals.
Asunto(s)
Ácidos Aminosalicílicos/metabolismo , Heces/química , Ácidos Aminosalicílicos/farmacología , Ácidos Aminosalicílicos/uso terapéutico , Ácidos Aminosalicílicos/orina , Cromatografía Líquida de Alta Presión , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/metabolismo , Hemoglobinas/metabolismo , Humanos , Peróxido de Hidrógeno/metabolismo , Hidróxidos/metabolismo , Ácido Hipocloroso , Técnicas In Vitro , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Mesalamina , Oxidación-Reducción , Espectrofotometría Ultravioleta , Relación Estructura-ActividadRESUMEN
Single unit activity was recorded from the suprachiasmatic nucleus (SCN) and preoptic/anterior hypothalamus (POAH) of unrestrained Wistar rats during sleep and wakefulness. Regularly firing cells, which are abundant in in vitro SCN preparations and have been considered the basis of a central neuronal oscillator, were conspicuously absent in this preparation and in other in vivo studies. Most of the 55 cells recorded in the SCN and POAH were characterized by spontaneous firing rates below 12 Hz and with heterogeneous patterns of changes in frequency with arousal states. In vivo neurophysiological studies of the SCN in which the anesthetic agent urethane is used should consider the effect of different levels of arousal, as indicated by the cortical EEG, in evaluating the relationship between sensory stimulation and single unit activity.
Asunto(s)
Hipotálamo Anterior/fisiología , Área Preóptica/fisiología , Sueño/fisiología , Núcleo Supraquiasmático/fisiología , Vigilia/fisiología , Potenciales de Acción , Animales , Mapeo Encefálico , Masculino , Ratas , Ratas EndogámicasRESUMEN
Male mice were subjected to repeated inhalation exposures to different concentrations (165, 204, 250, or 300 ppm) of ethylene oxide (EtO) during an 8.5-week period. Transmitted clastogenic effects of these exposures were measured in terms of induction of dominant lethal mutations and heritable translocations. The concentration-response curves for both endpoints are not linear but are markedly concave upward. Significant increases in dominant lethals were detected at all concentrations, except the lowest one. In comparison, the incidences of heritable translocations were significantly increased at all concentrations.
Asunto(s)
Óxido de Etileno/toxicidad , Mutación , Translocación Genética , Administración por Inhalación , Animales , Relación Dosis-Respuesta a Droga , Óxido de Etileno/administración & dosificación , Incidencia , Masculino , Ratones , Ratones Endogámicos C3H , MutágenosRESUMEN
Calcium cyclamate, an artificial sweetener, was studied for its effectiveness in inducing transmissible chromosomal aberrations in germ cells of male mice. Both the dominant-lethal and the heritable translocation tests were carried out following daily treatment (on weekdays) of males by oral intubation with the maximum tolerated dose for 6 weeks. Calcium cyclamate is negative in both tests; therefore, there is no evidence of induced chromosome breakage and exchange.
Asunto(s)
Ciclamatos/farmacología , Genes Dominantes/efectos de los fármacos , Genes Letales/efectos de los fármacos , Translocación Genética/efectos de los fármacos , Animales , Aberraciones Cromosómicas , Ciclamatos/toxicidad , Masculino , Ratones , Ratones Endogámicos C3H , Ratones Endogámicos C57BLRESUMEN
Bulk electrolysis of the antioxidant flavonoids quercetin and kaempferol in acetonitrile both yield a single oxidation product in two-electron processes. The oxidation products are more polar than their parent compounds, with an increased molecular weight of 16g/mol, and were identified as 2-(3,4-dihydroxybenzoyl)-2,4,6-trihydroxy-3(2H)-benzofuranone and 2-(4-hydroxybenzoyl)-2,4,6-trihydroxy-3(2H)-benzofuranone for quercetin and kaempferol, respectively. Two-electron oxidation of the parent flavonoid is suggested to yield a 3,4-flavandione with unchanged substitution pattern in the A- and B-ring, which may rearrange to form the substituted 3(2H)-benzofuranone through the chalcan-trione ring-chain tautomer. The acidity of the 3-OH group is suggested to determine the fate of the flavonoid phenoxyl radical, originally formed by one-electron oxidation, as no well-defined oxidation product of luteolin (lacking the 3-OH group) could be isolated despite rather similar half-peak potentials: Ep/2 = 0.97V, 0.98 V and 1.17 V vs. NHE for quercetin, kaempferol and luteolin, respectively, as measured by cyclic voltammetry in acetonitrile.
Asunto(s)
Benzofuranos/metabolismo , Electrólisis , Electrones , Quempferoles , Quercetina/análogos & derivados , Quercetina/metabolismo , Benzofuranos/química , Cromatografía Líquida de Alta Presión , Flavonoides/química , Flavonoides/metabolismo , Luteolina , Espectrometría de Masas , Resonancia Magnética Nuclear Biomolecular , Oxidación-Reducción , Quercetina/química , Espectrofotometría Ultravioleta , Factores de TiempoRESUMEN
Investigation of the ethanolic extracts from Phytolacca rivinoides and P. bogotensis has resulted in the isolation of five new triterpenoid glycosides of serjanic acid. Their structures have been established mainly by spectroscopic methods (FAB-MS, 1H, 13C NMR, COSY, NOESY, TOCSY, HETCOR and J-resolved 1H NMR) as 3-O-(O-beta-D-galactopyranosyl-(1-->3)-O-beta-D-glucopyranosyl)serjan ic acid 28-O-beta-D-glucopyranosyl ester, 3-O-(O-beta-D-glucopyranosyl-(1-->3)-O-[beta-D-galactopyranosyl-(1-->4)] -O- beta-D-glucopyranosyl)serjanic acid 28-O-beta-D-glucopyranosyl ester, 3-O-(O-alpha-L-rhamnopyranosyl-(1-->2)-O-beta-D-glucopyranosyl-(1-->2)- O-beta-glucopyranosyl)serjanic acid 28-O-beta-D-glucopyranosyl ester, 3-O-(O-beta-D-glucopyranosyl-(1-->3)-O-beta-D-galactopyranosyl-(1-->4)- O-beta-D-glucopyranosyl)serjanic acid 28-O-beta-D-glucopyranosyl ester and 3-O-(O-beta-D-galactopyranosyl-(1-->4)-O-[beta-D-glucopyranosyl-(1-->3)] - O-beta-D-glucopyranosyl)serjanic acid.
Asunto(s)
Plantas Medicinales/química , Saponinas/aislamiento & purificación , Triterpenos/aislamiento & purificación , Secuencia de Carbohidratos , Espectroscopía de Resonancia Magnética , Datos de Secuencia Molecular , Saponinas/química , Espectrometría de Masa Bombardeada por Átomos Veloces , Triterpenos/químicaRESUMEN
Three new monodesmosidic saponins, all glycosides of 2 beta-hydroxyoleanolic acid, were isolated from an aqueous extract of a Zimbabwean strain of Phytolacca dodecandra. Their structures were, mainly by spectroscopic methods (LSIMS, 1H NMR, COSY, NOESY, TOCSY, J-resolved 1H NMR, 13C NMR, HETCOR), established as 3-O-[2',4'-di-O-(beta-D-glucopyranosyl)-beta-D-glucopyranosyl]2 beta-hydroxyoleanolic acid, 3-O-[O-alpha-L-rhamnopyranosyl-(1-->2)-O-[beta-D-galactopyranosyl- (1-->3)]-beta-D-glucopyranosyl]2 beta-hydroxyoleanolic acid and 3-O-[3'-O-(beta-D-galactopyranosyl)-beta-D-glucopyranosyl]2 beta-hydroxyoleanolic acid. Two of the saponins were submitted to a preliminary screening for molluscicidal activity against the schistosomiasis transmitting snail Biomphalaria glabrata and showed, respectively, strong and weak activity. In addition, four saponins previously reported from other strains of Phytolacca dodecandra were identified.
Asunto(s)
Moluscocidas/aislamiento & purificación , Plantas/química , Saponinas/aislamiento & purificación , Animales , Biomphalaria , Secuencia de Carbohidratos , Bovinos , Proteínas Hemolisinas/aislamiento & purificación , Técnicas In Vitro , Espectroscopía de Resonancia Magnética , Datos de Secuencia Molecular , Estructura Molecular , ZimbabweRESUMEN
Two new saponins were isolated from the fruits of Catunaregam nilotica Stapf, syn. Lachnosiphonium nilotica; Randia nilotica; Xeromphis nilotica. Their structures were determined mainly by spectroscopic methods as 3- O-[O-alpha-L-rhamnopyranosyl-(1-->3)-O-[O-beta-D-glucopyranosyl-(1 -->3)]- beta-D-glucopyranosyl]oleanolic acid and 28-O-beta-D- glucopyranosyl-3-O-[O-alpha-L-rhamnopyranosyl-(1-->3)-O[O-beta-D- glucopyranosyl]-beta-D-glycopyranosyl]oleanolate. The monodesmosidic saponin is a potent molluscicide against the schistosomiasis transmitting snail Biomphalaria glabrata with a LC50 value of 3 ppm. In addition two known saponins, 3-O-[2', 3'-di-O-(beta-D-glucopyranosyl)-beta-D- glucopyranosyl]oleanolic acid and 3-O-[O-beta-D-glucopyranosyl(1-->3)- beta-D-glucopyranosyl]oleanolic acid, were identified and their molluscicidal activity determined, the LC50 values being 26 and 3 ppm, respectively. Initial molluscicidal screening of the crude water and ethanol extracts revealed 100% snail mortality at concentrations of 100 and 50 ppm, respectively. The haemolytic activity of the molluscicidal saponins was determined as well and the HC50 values towards bovine erythrocytes found to be 3 ppm for the new saponin, and 16 and 2 ppm, respectively, for the two known saponins.
Asunto(s)
Moluscocidas/aislamiento & purificación , Ácido Oleanólico/análogos & derivados , Saponinas/aislamiento & purificación , Árboles/química , Animales , Secuencia de Carbohidratos , Espectroscopía de Resonancia Magnética , Datos de Secuencia Molecular , Moluscocidas/química , Moluscocidas/farmacología , Saponinas/química , Saponinas/farmacologíaRESUMEN
1. para-Fluoro-hexahydrosila-difenidol (p-F-HHSiD) has been proposed as an M3 selective antagonist. However, the M3 selectivity is variable in that it exhibits a high pA2 value for M3 muscarinic receptors in guinea-pig ileum but a low value at muscarinic receptors in guinea-pig trachea. 2. The pA2 value in the trachea was found to be agonist independent since similar pA2 values were found when acetylcholine, carbachol, (+)-cis-dioxolane or OXA-22 were used (7.13, 7.03, 6.85 and 6.97, respectively). The pA2 value was not meaningfully increased when the equilibrium period was increased from 60 to 180 min. The pA2 value was unaffected by blockade of M1 or M2 receptors, using 0.1 microM pirenzepine or methoctramine (7.03 and 7.14, respectively). p-F-HHSiD and atropine appeared to act at the same site, as adjudged by combination concentration-ratio studies. 3. The pA2 values for p-F-HHSiD vary by 10 fold between ileal (8.0) and tracheal M3 receptors (7.0). The precise reason for this is unknown, but appears to be unrelated to conditions of disequilibrium that could be detected. The antagonist should therefore only be employed to distinguish M3 or M1 from M2 receptors. In this respect, although the M1/M3 vs M2 discrimination is relatively large (68 fold), p-F-HHSiD exhibits similar properties to other putative M3 selective antagonists such as 4-diphenylacetoxy-N-methyl piperidine methiodide (4-DAMP) or the parent compound, hexahydrosiladifenidol (HHSiD).
Asunto(s)
Músculo Liso/metabolismo , Parasimpatolíticos/farmacología , Piperidinas/farmacología , Receptores Muscarínicos/efectos de los fármacos , Animales , Cobayas , Técnicas In Vitro , Contracción Isométrica , Masculino , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Parasimpaticomiméticos/farmacología , Tráquea/efectos de los fármacos , Tráquea/metabolismoRESUMEN
Four elements that have been implicated in free-radical-induced oxidative stress in Alzheimer's disease (AD) were measured by instrumental neutron activation analysis (INAA) in seven brain regions from 58 AD patients and 21 control subjects. A statistically significant elevation of iron and zinc was observed in multiple regions of AD brain, compared with controls. Mercury was elevated in AD in most regions studied, but the high variability of mercury levels in both AD and control subjects prevented the AD-control difference from reaching significance. Selenium, a protective agent against mercury toxicity, was significantly elevated only in AD amygdala. The elevation of iron and zinc in AD brain has the potential of augmenting neuron degeneration through free radical processes.
Asunto(s)
Enfermedad de Alzheimer/metabolismo , Encéfalo/metabolismo , Estrés Oxidativo/fisiología , Oligoelementos/metabolismo , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Estudios de Casos y Controles , Femenino , Humanos , Hierro/metabolismo , Kentucky , Masculino , Mercurio/metabolismo , Persona de Mediana Edad , Selenio/metabolismo , Zinc/metabolismoRESUMEN
In a previous report (Generoso et al., 1985) it was shown that the two hybrid stocks of mice, (C3H/R1 x 101/R1)F1 and (SEC/R1 x C57BL/6)F1, differed in their responses to induction of chromosomal aberrations following exposure of the stem-cell spermatogonia to 500 R x 4 (4-week intervals) acute X-rays. The levels of response in the two stocks were paralleled by the effects on the length of the sterile period, which presumably results from stem-cell killing and repopulation. The present study was conducted in order to determine whether the differences between the two stocks in these parameters hold true also for other conditions of radiation exposure. Thus, comparative experiments were conducted using the following acute exposure regimens: 500 R single dose, 500 R + 500 R (24-h interval), 100 R + 900 R (24-h interval), and 500 R x 4 (8-week intervals). The endpoints measured were chromosome rearrangements in diakinesis/metaphase-I meiocytes, embryonic lethality in conceptuses, length of sterile period and testis weight. Trend analysis indicated that higher frequencies of chromosome rearrangements and embryonic lethality were recovered from (C3H/R1 x 101/R1)F1 than from (SEC/R1 x C57BL/6)F1 males, that there were no significant differences between stocks in testis weight reductions, and that there was no consistency in the direction of the significant differences that occurred in the length of the sterile period. A definitive conclusion regarding the possible association between induction of chromosomal aberrations and induction of cell killing awaits direct histological analysis of the stem-cell population.
Asunto(s)
Aberraciones Cromosómicas , Espermatogonias/efectos de la radiación , Testículo/efectos de la radiación , Animales , Relación Dosis-Respuesta en la Radiación , Embrión de Mamíferos/efectos de la radiación , Infertilidad Masculina , Masculino , Ratones , Células Madre/efectos de la radiación , Translocación GenéticaRESUMEN
This study was conducted to estimate the frequency of transmitted reciprocal translocations per rad of exposure to alpha particles from [239Pu]citrate. Data indicate that the rate of induction of heritable translocations is related linearly to the duration of spermatogonia stem cell exposure. The estimated increase in heritable translocations per rad of exposure of the stem cell to alpha particles is in the range of 1.45-2.91 X 10(-5)/gamete.
Asunto(s)
Aberraciones Cromosómicas/etiología , Plutonio , Translocación Genética , Animales , Aberraciones Cromosómicas/genética , Trastornos de los Cromosomas , Relación Dosis-Respuesta en la Radiación , Femenino , Infertilidad Masculina/etiología , Inyecciones Intravenosas , Masculino , Ratones , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Plutonio/administración & dosificación , Espermatogonias/efectos de la radiación , Testículo/efectos de la radiaciónRESUMEN
Although heritable translocations are an important endpoint for the assessment of genetic risk from radiation, there has been a serious information gap with regard to their induction in spermatogonial stem cells, the most important cell stage in males for risk considerations. This led to uncertainty in estimating the magnitude of risk per unit exposure. Further, the relationship between the frequency of reciprocal exchanges scored by cytological analysis of the exposed male's meiocytes and the frequency of those transmitted to first-generation offspring needed to be re-examined. In order to fill in these gaps, two radiation studies, i.e., dose response and dose fractionation, were conducted on spermatogonial stem cells in which heritable and cytologically detected translocations were scored. The present data are by far the most extensive, to date, for heritable translocation induction in spermatogonial stem cells. The linearity of the rising portion of the dose-effect curve and the additivity of effects observed in the fractionation study allow a direct estimation of the number of transmissible translocations expected per unit exposure. Thus, the expected increase in heritable translocations per rad of acute X-rays is 3.89 X 10(-5) per gamete. The data also show a lack of consistency between cytologically and genetically scored translocations.
Asunto(s)
Espermatogonias/efectos de la radiación , Espermatozoides/efectos de la radiación , Translocación Genética/efectos de la radiación , Animales , Relación Dosis-Respuesta en la Radiación , Fertilización , Masculino , Ratones , Espermatogénesis/efectos de la radiación , Rayos XRESUMEN
Ionizing radiation induces balanced reciprocal translocations in spermatogonial stem cells of mice. From cells carrying these rearrangements, which can be scored cytologically in the diakinesis-metaphase I stage, balanced normal, balanced translocated and unbalanced (duplication/deficiency) sperm can be produced. The relationship between expected (calculated from cytological data) and observed frequencies of embryonic lethality (presumably as a result of unbalanced sperm fertilizing the egg) following exposure of spermatogonial stem cells to X-rays was studied in two hybrid stocks. A marked difference in the incidence of induced embryonic lethality was found between the two stocks. Similarly, a difference in the cytological frequencies of translocations was also found, although smaller than that observed for embryonic lethality. Thus, it appears that the difference between the two stocks in the frequencies of embryonic lethality may be attributable both to processes occurring prior to metaphase I and to a difference in the rate of transmission of unbalanced chromosome constitutions.