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美司钠(2-巯基乙烷磺酸盐)与环磷酰胺在体内外致突变性的相互作用。

Interaction of Mesna (2-mercaptoethane sulfonate) with the mutagenicity of cyclophosphamide in vitro and in vivo.

作者信息

Lähdetie J, Räty R, Sorsa M

机构信息

Department of Medical Genetics, University of Turku, Finland.

出版信息

Mutat Res. 1990 Sep;245(1):27-32. doi: 10.1016/0165-7992(90)90021-b.

DOI:10.1016/0165-7992(90)90021-b
PMID:2118231
Abstract

The effects of sodium 2-mercaptoethane sulfonate (Mesna) on the mutagenicity of cyclophosphamide (CP) were assessed in vitro by the Ames test and in vivo in rats by analyzing micronuclei in bone marrow and mutagenic activity in urine. Mesna alone was negative in all test systems, while CP gave a positive response in all of them. In a combined treatment there was no significant reduction of the CP-induced mutagenicity in Salmonella. In rats the frequency of bone marrow micronuclei was not diminished when Mesna was given together with CP. May-Grunwald-Giemsa staining and Hoechst-Pyronin fluorescent staining techniques for micronuclei yielded similar results. The urine of rats treated with CP was mutagenic to Salmonella and no significant difference was observed when the rats had received both Mesna and CP. The results give support to the theory that Mesna acts primarily by reducing the toxicity of metabolites of CP, particularly acrolein, in the urinary tract and not by suppressing the mutagenicity of the active metabolites of CP.

摘要

通过艾姆斯试验在体外评估了2-巯基乙烷磺酸钠(美司钠)对环磷酰胺(CP)致突变性的影响,并通过分析大鼠骨髓中的微核和尿液中的诱变活性在体内进行了评估。单独使用美司钠在所有测试系统中均呈阴性,而CP在所有测试系统中均呈阳性反应。在联合治疗中,CP诱导的沙门氏菌致突变性没有显著降低。在大鼠中,当美司钠与CP一起给药时,骨髓微核的频率没有降低。用于微核的May-Grunwald-Giemsa染色和Hoechst-Pyronin荧光染色技术产生了相似的结果。用CP处理的大鼠尿液对沙门氏菌具有诱变性,当大鼠同时接受美司钠和CP时,未观察到显著差异。这些结果支持了这样一种理论,即美司钠主要通过降低CP代谢产物(特别是丙烯醛)在尿路中的毒性起作用,而不是通过抑制CP活性代谢产物的诱变性起作用。

相似文献

1
Interaction of Mesna (2-mercaptoethane sulfonate) with the mutagenicity of cyclophosphamide in vitro and in vivo.美司钠(2-巯基乙烷磺酸盐)与环磷酰胺在体内外致突变性的相互作用。
Mutat Res. 1990 Sep;245(1):27-32. doi: 10.1016/0165-7992(90)90021-b.
2
In vitro/in vivo effects of Mesna on the genotoxicity and toxicity of cyclophosphamide--a study aimed at clarifying the mechanism of Mesna's anticarcinogenic activity.美司钠对环磷酰胺遗传毒性和毒性的体外/体内作用——一项旨在阐明美司钠抗癌活性机制的研究。
Toxicol Lett. 1988 Apr;41(1):49-56. doi: 10.1016/0378-4274(88)90007-0.
3
Effect of the uroprotector sodium 2-mercaptoethane sulfonate (Mesna) on the proliferation of the bladder urothelium in the rat after administration of cyclophosphamide.巯乙磺酸钠(美司钠)对环磷酰胺给药后大鼠膀胱尿路上皮增殖的影响。
Urol Int. 1984;39(2):61-7. doi: 10.1159/000280947.
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Attenuation of cytogenetic damage by 2-mercaptoethanesulfonate in cultured human lymphocytes exposed to cyclophosphamide and its reactive metabolites.在暴露于环磷酰胺及其活性代谢产物的培养人淋巴细胞中,2-巯基乙烷磺酸盐对细胞遗传损伤的减轻作用。
Cancer Res. 1986 Jan;46(1):203-10.
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Sodium 2-mercaptoethane sulfonate protection against cyclophosphamide-induced teratogenicity in rats.2-巯基乙烷磺酸钠对环磷酰胺诱导的大鼠致畸作用的保护作用。
Toxicol Appl Pharmacol. 1986 Jan;82(1):80-6. doi: 10.1016/0041-008x(86)90440-0.
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Prevention of urinary bladder tumors in cyclophosphamide-treated rats by additional medication with the uroprotectors sodium 2-mercaptoethane sulfonate (mesna) and disodium 2,2'-dithio-bis-ethane sulfonate (dimesna).通过额外给予尿路保护剂2-巯基乙烷磺酸钠(美司钠)和2,2'-二硫代双乙烷磺酸钠(二巯基丁二酸钠)预防环磷酰胺治疗大鼠的膀胱肿瘤。
Cancer. 1983 Feb 15;51(4):606-9. doi: 10.1002/1097-0142(19830215)51:4<606::aid-cncr2820510409>3.0.co;2-s.
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Studies on the urotoxicity of oxazaphosphorine cytostatics and its prevention--III. Profile of action of sodium 2-mercaptoethane sulfonate (mesna).氮杂磷三环类细胞抑制剂的尿路毒性及其预防研究——III. 2-巯基乙烷磺酸钠(美司钠)的作用概况。
Eur J Cancer Clin Oncol. 1982 Dec;18(12):1377-87. doi: 10.1016/0277-5379(82)90143-2.
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[Prevention of tumor formation in the bladder by sodium-2-mercaptoethane sulfonate (mesna). Experimental studies and clinical consequences].[2-巯基乙烷磺酸钠(美司钠)预防膀胱肿瘤形成。实验研究及临床结果]
Urologe A. 1984 Sep;23(5):291-6.
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[Prevention of urotoxic actions of cyclophosphamide and ifosfamide by dimesna (preliminary communication) (author's transl)].二巯基丁二酸钠预防环磷酰胺和异环磷酰胺的尿路毒性作用(初步报告)(作者译)
Arzneimittelforschung. 1982;32(5):486-7.
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Comparison of reduced glutathione with 2-mercaptoethane sulfonate to prevent cyclophosphamide-induced urotoxicity.还原型谷胱甘肽与2-巯基乙烷磺酸盐预防环磷酰胺诱导的尿路毒性的比较。
Cancer Lett. 1986 Jul;32(1):1-6. doi: 10.1016/0304-3835(86)90032-7.

引用本文的文献

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Exposure to the Dietary Supplement N-Acetyl-L-Cysteine during Pregnancy Reduces Cyclophosphamide Teratogenesis in ICR Mice.孕期接触膳食补充剂N-乙酰-L-半胱氨酸可降低环磷酰胺对ICR小鼠的致畸作用。
J Clin Nutr Food Sci. 2018;1(1):035-39. Epub 2018 Oct 18.
2
Mesna (2-mercaptoethane sodium sulfonate) functions as a regulator of myeloperoxidase.美司钠(2-巯基乙烷磺酸钠)作为髓过氧化物酶的调节剂发挥作用。
Free Radic Biol Med. 2017 Sep;110:54-62. doi: 10.1016/j.freeradbiomed.2017.05.019. Epub 2017 May 25.