RESUMEN
A major activity of the lumber industry is the kiln-drying of wood. In order to ascertain whether wood-drying condensates pose a possible environmental hazard, the cytotoxicity and genotoxicity of these condensates in vitro, were tested using an assay validated using Chinese hamster ovary (CHO) cells and a known genotoxicant, mitomycin C. Subsequently, the assay was developed for the human peripheral blood lymphocyte (HPBL) system, as it was felt that results derived from human cells would reflect the situation more closely in vivo. Condensates from Southern yellow pine, Eastern white pine and Douglas fir trees were tested in CHO and HPBL systems and have demonstrated cytotoxic and genotoxic effects in vitro, as reported elsewhere. Red oak condensate has also been tested using the HPBL system. Thus far, results are consistent with the hypothesis that there is no difference between the cytotoxic and genotoxic effects of treated cells versus controls. This finding indicates either that the condensate of red oak poses no appreciable genetic hazard as measured by cytotoxicity and genotoxicity assays, or that the condensate has lost its potency with time and storage; both of these possibilities have important environmental implications.
Asunto(s)
Contaminantes Ocupacionales del Aire/toxicidad , Contaminantes Atmosféricos/toxicidad , Células CHO/efectos de los fármacos , Residuos Industriales/efectos adversos , Linfocitos/efectos de los fármacos , Pruebas de Mutagenicidad , Madera , Animales , Células Cultivadas , Aberraciones Cromosómicas , Cricetinae , Cricetulus , Calor , Humanos , Índice Mitótico/efectos de los fármacos , Intercambio de Cromátides Hermanas/efectos de los fármacos , Especificidad de la Especie , Factores de Tiempo , VolatilizaciónRESUMEN
The outcome of in utero cocaine exposure is unclear. To determine if cocaine affects neuronal growth and differentiation, we used PC-12 cells, which have a mitogenic response to IGF-I and differentiate into neurons on exposure to nerve growth factor. Differentiation was quantified as neurite extension after a 72-h exposure to 20 ng/ml nerve growth factor (dosage at 50% maximal effectiveness) and cocaine doses ranging from 0.01 to 10 micrograms/ml. The results were 49 +/- 2, 40 +/- 3, 29 +/- 2, 23 +/- 2, and 12 +/- 2% differentiation with respective cocaine concentrations of 0, 0.01, 0.1, 1, and 10 micrograms/ml (P < 0.0001). Cocaine stability studies showed insignificant spontaneous hydrolysis under the conditions of this study. Cocaine did not affect cell viability or number, but had a relatively modest, statistically significant (P < 0.001) inhibitory effect on IGF-I-stimulated thymidine incorporation. The dose-response curves for differentiation vs mitogenic response differed significantly (P = 0.021). Therefore, cocaine inhibition of these processes is probably mediated by different mechanisms, and not caused by generalized toxicity. To our knowledge, this is the first demonstration of cocaine effects on neuronal multiplication and differentiation in vitro. The results suggest in utero exposure may directly impair brain development.
Asunto(s)
Cocaína/farmacología , Neuronas/efectos de los fármacos , Animales , Diferenciación Celular/efectos de los fármacos , División Celular/efectos de los fármacos , ADN/biosíntesis , Relación Dosis-Respuesta a Droga , Estabilidad de Medicamentos , Factores de Crecimiento Nervioso/farmacología , Ratas , Células Tumorales CultivadasRESUMEN
Potentiation of renin release can be achieved by combining adrenergic stimulation and renal vasodilatation. To examine whether pentobarbital anesthesia influences plasma renin concentration (PRC) by its vasodilatory effect, experiments were performed in rats subjected to increasing levels of adrenergic activity. PRC was two- to fourfold higher in anesthetized than in conscious rats when the beta-adrenoceptor agonist isoproterenol HCl (0.05-3.2 micrograms kg-1 min-1) was infused. The sympathomimetic agent tyramine suppressed and the alpha-adrenoceptor blocker phenoxybenzamine enhanced to the same extent the isoproterenol-stimulated PRC in conscious and anesthetized animals. Chronic renal denervation did not abolish the isoproterenol-pentobarbital synergistic effect on PRC. These results are consistent with the view that the renin response to pentobarbital anesthesia is somehow related to the vascular effects of the anesthetic.
Asunto(s)
Riñón/metabolismo , Pentobarbital/farmacología , Renina/sangre , Animales , Presión Sanguínea/efectos de los fármacos , Femenino , Isoproterenol/farmacología , Riñón/irrigación sanguínea , Fenoxibenzamina/farmacología , Propranolol/farmacología , Ratas , Receptores Adrenérgicos beta/fisiología , Renina/metabolismo , Tiramina/farmacología , VasodilataciónRESUMEN
Studies were undertaken in intact rats to characterize the renin response to pentobarbital anesthesia and the mechanisms involved in this response. Aortic and peritoneal cavity cannulas were previously implanted to allow drug infusion, blood sampling and anesthesia to be performed without stress. A sustained 2-3-fold increase in plasma renin concentration (PRC) and a 10-15 mm Hg depression of mean arterial pressure were found in pentobarbital anesthesia. Circulating levels of epinephrine and norepinephrine were unchanged. Sympathetic stimulation by tyramine did not decrease and chronic renal denervation did not abolish the PRC rise by pentobarbital. Phenoxybenzamine given to conscious or anesthesized animals elevated PRC to similar levels. Propranolol was effective in suppressing PRC in anesthetized animals, regardless of the presence or absence of phenoxybenzamine. We concluded that the renin response to pentobarbital anesthesia is unrelated to changes in sympatho-adrenal activity. The response appears to be mediated by beta-adrenergic receptors. It is postulated that pentobarbital-induced relaxation of afferent arterioles or JG cells exposes previously concealed beta-receptor sites which increase the signal for the release of renin.