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钼盐在体外人体细胞和体内小鼠中的遗传毒性研究。

Studies on the genotoxicity of molybdenum salts in human cells in vitro and in mice in vivo.

作者信息

Titenko-Holland N, Shao J, Zhang L, Xi L, Ngo H, Shang N, Smith M T

机构信息

Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley 94720-7360, USA.

出版信息

Environ Mol Mutagen. 1998;32(3):251-9. doi: 10.1002/(sici)1098-2280(1998)32:3<251::aid-em8>3.0.co;2-r.

Abstract

Molybdenum is an essential element in plants and animals as a cofactor for enzymes. Molybdenum trioxide is used in metallurgical processes, in cosmetics as a pigment, and in contact lens solution, yet limited information is available on molybdenum genotoxicity. In the present study the micronucleus (MN) assay in human lymphocytes and mouse bone marrow and the dominant lethal assay in mice were used to assess the genotoxic effects of molybdenum salts in vitro and in vivo. Two salts of molybdenum were tested in whole blood cultures. Ammonium molybdate was more potent than sodium molybdate in causing a dose-dependent decrease in viability and replicative index and an increase in MN formation in binucleated lymphocytes (P < 0.001). A dose-response in both kinetochore-positive MN (caused by chromosome lagging) and kinetochore-negative MN (associated with chromosome breakage) was observed. Based on the results of a toxicity study of sodium molybdate, two doses, 200 and 400 mg/kg, were assessed in the bone marrow MN assay in mice (two i.p. injections 24 and 48 hr prior to euthanasia). A modest but statistically significant increase in MN frequency in polychromatic erythrocytes was observed (P < 0.05). The same treatment protocol was used to analyze dominant lethality. A dose-dependent increase in postimplantation loss represented mostly by early resorptions was observed the first week after treatment (P = 0.003). These preliminary data suggest that sodium molybdate induces dominant lethality at the postmeiotic stage of spermatogenesis. Overall, molybdenum salts produced moderately positive results both in vitro in human cells and in vivo in mice.

摘要

钼作为酶的辅助因子,是动植物体内的必需元素。三氧化钼用于冶金过程、化妆品中的色素以及隐形眼镜护理液中,然而关于钼的遗传毒性的信息有限。在本研究中,采用人淋巴细胞和小鼠骨髓中的微核(MN)试验以及小鼠中的显性致死试验,来评估钼盐在体外和体内的遗传毒性作用。在全血培养中测试了两种钼盐。钼酸铵在导致双核淋巴细胞活力和复制指数呈剂量依赖性下降以及微核形成增加方面比钼酸钠更具效力(P < 0.001)。观察到动粒阳性微核(由染色体滞后引起)和动粒阴性微核(与染色体断裂相关)均呈剂量反应。基于钼酸钠的毒性研究结果,在小鼠骨髓微核试验中评估了200和400 mg/kg两个剂量(在安乐死前提早24和48小时腹腔注射两次)。观察到多染性红细胞中微核频率有适度但具有统计学意义的增加(P < 0.05)。采用相同的处理方案来分析显性致死性。在处理后的第一周观察到植入后损失呈剂量依赖性增加,主要表现为早期吸收(P = 0.003)。这些初步数据表明钼酸钠在精子发生的减数分裂后阶段诱导显性致死性。总体而言,钼盐在体外人细胞和体内小鼠中均产生了中度阳性结果。

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