当前位置: X-MOL 学术Mutat. Res. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
In vitro and in vivo genotoxicity assessment of ferric ferrocyanide and potassium-cobalt ferrocyanide
Mutation Research/Genetic Toxicology and Environmental Mutagenesis ( IF 1.9 ) Pub Date : 2020-09-07 , DOI: 10.1016/j.mrgentox.2020.503235
S Simar-Meintières 1 , P Guigon 2 , F Nesslany 3
Affiliation  

Ferric hexacyanoferrate(II) (Fe4[Fe(CN)6]3), i.e. Prussian blue (PB) has been used for many years to remove from the body the two toxic isotopes of cesium and thallium following irradiation.

Recently, potassium cobalt hexacyanoferrate(II) (K2COFe(CN)6), which has shown a better efficacy for decontamination, is also being considered for use to enhance the elimination of cesium isotopes. In view to its preclinical and clinical development, in vitro and in vivo GLP-compliant genotoxicity studies were carried out on this product as well as on PB for comparison. Several tests dissecting the main events leading to genotoxicity, i.e. mutagenicity and chromosomal aberrations, both structural and quantitative were implemented.

In vitro, no mutagenic effect was observed in the Ames test but both compounds were positive in the mouse lymphoma assay on TK locus and induced clastogenic effects in the in vitro chromosomal aberrations test on human lymphocytes, either in absence or in presence of metabolic activation.

K-Co-ferrocyanide was also assayed in vivo in the mouse bone marrow micronucleus assay and PB was assessed for DNA fragmentation in the rodent Comet assay in both glandular stomach and colon. In the in vivo micronucleus mouse bone marrow, K-Co-ferrocyanide did not display any genotoxic activity up to 2000 mg/kg/d (x2) by oral route. In opposite, PB induced a significant increase in DNA fragmentation both in the glandular stomach and in the colon of rat treated 3 times with intake ranging from 2000 to 500 mg/kg. PB should be considered as an in vivo mutagen as well as Potassium cobalt hexacyanoferrate(II) since the in vitro genotoxicity profiles of both ferrocyanides are quite similar.

Their use as cesium/ thallium decontamination agents in human should be assessed following a benefit/risk approach to enable a robust decision-making.



中文翻译:

亚铁氰化铁和亚铁氰化钾钴的体外和体内遗传毒性评估

六氰基铁酸铁(II) (Fe 4 [Fe(CN) 6 ] 3 ),普鲁士蓝(PB) 多年来一直被用于在辐射后从体内去除铯和铊这两种有毒同位素。

最近,六氰基铁酸钴钾(II) (K 2 COFe(CN) 6 ) 已显示出更好的去污效果,也正在考虑用于增强铯同位素的消除。鉴于其临床前和临床开发,对该产品以及 PB 进行了体外体内符合 GLP 的基因毒性研究以进行比较。实施了几项分析导致遗传毒性的主要事件,致突变性和染色体畸变的试验,包括结构和定量。

在体外,在 Ames 试验中未观察到致突变作用,但两种化合物在 TK 基因座的小鼠淋巴瘤试验中均呈阳性,并在体外染色体畸变试验中对人淋巴细胞的诱导致裂作用,无论是否存在代谢激活。

K-Co-亚铁氰化物也在小鼠骨髓微核试验中进行了体内试验,并且在啮齿动物彗星试验中在腺胃和结肠中评估了PB的DNA断裂。在体内微核小鼠骨髓中,K-Co-亚铁氰化物通过口服途径在高达 2000 mg/kg/d (x2) 时未显示任何基因毒性活性。相反,PB 诱导大鼠腺胃和结肠中 DNA 断裂的显着增加,摄入量范围为 2000 至 500 mg/kg。PB 应被视为体内诱变剂以及六氰基铁酸钾 (II),因为这两种亚铁氰化物的体外遗传毒性特征非常相似。

它们在人体中作为铯/铊净化剂的使用应按照收益/风险方法进行评估,以做出稳健的决策。

更新日期:2020-09-15
down
wechat
bug