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首页> 外文期刊>Journal of applied toxicology >Metabolic fate of ultratrace levels of GeCl(4) in the rat and in vitro studies on its basal cytotoxicity and carcinogenic potential in Balb/3T3 and HaCaT cell linesdagger.
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Metabolic fate of ultratrace levels of GeCl(4) in the rat and in vitro studies on its basal cytotoxicity and carcinogenic potential in Balb/3T3 and HaCaT cell linesdagger.

机译:大鼠中微量GeCl(4)的代谢命运以及在Balb / 3T3和HaCaT细胞系匕首中其基础细胞毒性和致癌潜力的体外研究。

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摘要

The use of germanium (Ge) and the possibility of exposure to trace and ultratrace amounts of this element is increasing. Germanium is widely used in the industrial field as a semiconductor and also as a dietary supplement, an elixir to 'promote health and cure disease' (e.g. cancer and AIDS). More recently, germanium nanoparticles, ranging in size from 60 to 80 nm, have been developed as a potential spleen imaging agent. Like other metal-based nanoparticles used in nanomedicine, Ge nanoparticles may release trace and ultratrace amounts of Ge ions when injected. The metabolic fate and toxicity of these ions still needs to be evaluated. In this study the metabolic fate of a cationic tetravalent Ge species was studied in vivo by injecting rats i.p. with ultratrace amounts of Ge (80 ng kg(-1)) as [(68)Ge]GeCl(4). The cytotoxicity and carcinogenic potential was assessed in vitro using immortalised human skin keratinocytes and mouse fibroblasts (HaCaT and Balb/c 3T3 cell lines, respectively). At 24 h post-exposure Ge was poorly retained in rat tissues (kidney, liver, intestine, femur, spleen and the heart were the organs with the highest Ge concentration). In the blood, Ge was rapidly cleared, being almost equally distributed between plasma and red blood cells. The excretion was mainly via the urine. The hepatic and renal intracellular distribution showed the highest recovery of Ge in the cytosol and the nuclear fractions. Chromatographic separation and ultrafiltration experiments on kidney and liver cytosols showed that the bulk of Ge was associated with low molecular weight components, representing a 'mobile pool' of the element in the body. However, a significant part of the element was able to interact with biological macromolecules which could be responsible for the presence of Ge in the liver and kidney after 7 days. The in vitro experiments confirmed the low degree of cytotoxicity of GeCl(4) both in HaCaT and Balb/3T3. The latter model was more sensitive to the toxic effects induced by Ge as shown by a colony forming efficiency (CFE) greater than 70% at 700 microm of exposure. At the highest exposure concentration tested (700 microm) GeCl(4) failed to induce morphological neoplastic transformation of the cells, suggesting for the first time that a cationic form of Ge ions has no carcinogenic potential. This supports the results of the only study reported in mice, treated orally long-term to an anionic species of Ge such as sodium germanate (Kanisawa and Schroeder, 1967).
机译:锗(Ge)的使用以及暴露于痕量和超痕量该元素的可能性正在增加。锗在工业领域中广泛用作半导体,也作为膳食补充剂,是“促进健康和治愈疾病”(例如癌症和艾滋病)的灵丹妙药。最近,已开发出尺寸为60至80nm的锗纳米颗粒作为潜在的脾显像剂。像纳米药物中使用的其他基于金属的纳米粒子一样,Ge纳米粒子在注射时可能释放痕量和超痕量的Ge离子。这些离子的代谢命运和毒性仍然需要评估。在这项研究中,通过向大鼠腹膜内注射大鼠体内研究了阳离子四价锗物种的代谢命运。具有超痕量的Ge(80 ng kg(-1))作为[(68)Ge] GeCl(4)。使用永生化的人皮肤角质形成细胞和小鼠成纤维细胞(分别为HaCaT和Balb / c 3T3细胞系)在体外评估了细胞毒性和致癌潜力。暴露后24 h,Ge在大鼠组织中的保留率很低(肾脏,肝脏,肠,股骨,脾脏和心脏是Ge浓度最高的器官)。在血液中,锗被迅速清除,几乎平均分布在血浆和红细胞之间。排泄主要是通过尿液。肝和肾细胞内分布显示在细胞质和核部分中Ge的回收率最高。在肾脏和肝脏细胞质上的色谱分离和超滤实验表明,大部分的Ge与低分子量成分有关,代表体内元素的“移动库”。然而,该元素的很大一部分能够与生物大分子相互作用,这可能是7天后肝脏和肾脏中存在Ge的原因。体外实验证实,在HaCaT和Balb / 3T3中,GeCl(4)的细胞毒性均较低。后一种模型对Ge诱导的毒性作用更为敏感,如暴露于700微米处的菌落形成效率(CFE)大于70%,则表明了这一点。在最高暴露浓度(700微米)下,GeCl(4)未能诱导细胞的形态学肿瘤转化,这首次表明阳离子形式的Ge离子没有致癌潜力。这支持了在小鼠中报告的唯一一项研究结果,该研究是对锗等阴离子物种(如锗酸钠)进行长期口服治疗的(Kanisawa和Schroeder,1967)。

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