Ríos J C, Repetto G, Jos A, del Peso A, Salguero M, Cameán A, Repetto M
National Institute of Toxicology, PO Box 863, 41080, Sevilla, Spain.
Toxicol In Vitro. 2003 Oct-Dec;17(5-6):635-41. doi: 10.1016/s0887-2333(03)00110-3.
Tribromophenol is a pesticide with fungicide activity, presently used as a replacement of pentachlorophenol as a wood preservative, and as a flame retardant in electronic and electrotechnical devices. Retinoic acid differentiated and non-differentiated SH-SY5Y human neuroblastoma cell cultures were exposed to a range of concentrations of tribromophenol for 24, 48 and 72 h and the effects evaluated at morphological, basal cytotoxicity and biochemical levels. Neuroblastoma cell number, evaluated by quantification of total protein content, was increasingly inhibited in accordance with the concentration of tribromophenol and the exposure time period. According to the mean effective concentrations, differentiated cultures were nearly three times more sensitive than naive cells. Lysosomal function evaluated by the neutral red uptake was stimulated, particularly in non-differentiated cells. MTS metabolization was stimulated by all the treatments, with more potency at 24 h for differentiated cells. Acetylcholinesterase activity increased with the time of exposure in non-differentiated cells, while in differentiated cells the activity was doubled at 24 h. Morphological alterations were evident from 12.5 microM, showing hydropic degeneration and reduction in cell number, and from that concentration, piknosis and apoptotic bodies were observed. In conclusion, the main effects detected for tribromophenol were the induction of neuroblastoma cell differentiation, as expressed by the inhibition of cell growth and the increase in acetylcholinesterase activity with a critical cell concentration of 0.1 microM. Apoptosis was observed at high concentrations. The induction of cell differentiation and the special sensitivity of differentiated cells can explain some mechanisms involved in the embryotoxic and foetotoxic potential of tribromophenol.
三溴苯酚是一种具有杀真菌活性的农药，目前用作木材防腐剂替代五氯苯酚，并用作电子和电气设备中的阻燃剂。将维甲酸分化和未分化的SH-SY5Y人神经母细胞瘤细胞培养物暴露于一系列浓度的三溴苯酚中24、48和72小时，并在形态、基础细胞毒性和生化水平上评估其效果。通过定量总蛋白含量评估的神经母细胞瘤细胞数量，随着三溴苯酚浓度和暴露时间段的增加而受到越来越大的抑制。根据平均有效浓度，分化培养物的敏感性几乎是未分化细胞的三倍。通过中性红摄取评估的溶酶体功能受到刺激，特别是在未分化细胞中。所有处理均刺激了MTS代谢，分化细胞在24小时时的效力更高。未分化细胞中乙酰胆碱酯酶活性随暴露时间增加，而在分化细胞中，该活性在24小时时加倍。从12.5 microM开始出现形态学改变，表现为细胞水肿变性和细胞数量减少，从该浓度开始，观察到核固缩和凋亡小体。总之，检测到的三溴苯酚的主要作用是诱导神经母细胞瘤细胞分化，表现为细胞生长抑制和乙酰胆碱酯酶活性增加，临界细胞浓度为0.1 microM。在高浓度下观察到凋亡。细胞分化的诱导以及分化细胞的特殊敏感性可以解释三溴苯酚胚胎毒性和胎儿毒性潜力的一些相关机制。
