抗肿瘤血清胸腺因子9肽的急性毒性和遗传毒性

doi:10.3969/j.issn.1004-616x.2022.01.011

癌变·畸变·突变 ›› 2022, Vol. 34 ›› Issue (1): 57-61.doi: 10.3969/j.issn.1004-616x.2022.01.011

抗肿瘤血清胸腺因子9肽的急性毒性和遗传毒性

杨玉^1,2, 黄雅理^2,3, 林飞², 汤龙²

1. 佳木斯大学基础医学院, 黑龙江佳木斯 154007;
2. 中国食品药品检定研究院, 北京 100050;
3. 海关总署国际检验检疫标准与技术法规研究中心, 北京 100013

收稿日期:2021-05-09 修回日期:2021-11-11 出版日期:2022-01-31 发布日期:2022-02-15
通讯作者: 汤龙,E-mail:tanglongybc@126.com E-mail:tanglongybc@126.com
作者简介:杨玉,E-mail:teacheryang2006@163.com
基金资助:
佳木斯大学青年创新人才培养支持计划项目（JMSUQP2020012）；黑龙江省卫生健康委科研课题（20210202040066）

Acute toxicity and genotoxicity of antitumor serum thymic factor 9 peptide

YANG Yu^1,2, HUANG Yali^2,3, LIN Fei², TANG Long²

1. Jiamusi University, College of Basic Medicine, Jiamusi 154007, Heilongjiang;
2. National Institutes for Food and Drug Control, Beijing 100050;
3. Research Center of International Inspection, Quarantine Standards and Technical Regulations in General Administration of Customs, Beijing 100013, China

Received:2021-05-09 Revised:2021-11-11 Online:2022-01-31 Published:2022-02-15

摘要/Abstract

摘要： 目的： 观察抗肿瘤创新药血清胸腺因子9肽是否存在急性毒性和遗传毒性，为临床用药提供安全性依据。方法： 小鼠、大鼠和Beagle犬一次性注射给予70.0 mg/kg血清胸腺因子9肽进行急性毒性试验，采用Ames试验、中国仓鼠肺成纤维细胞（CHL）染色体畸变试验和小鼠骨髓细胞微核试验组合进行血清胸腺因子9肽的遗传毒性试验。结果： 一次性注射给药后3种动物精神好、行为正常，均未出现兴奋或抑制体征，均未发现动物急性毒性表现；Ames试验在1~5 000 μg/皿浓度各菌株的平均回变菌落数均与溶剂对照组相似，未见明显增加（P>0.05）；CHL染色体畸变试验在1 400~5 600 μg/mL剂量范围内染色体畸变率均≤3%，与溶剂对照组比较，差异均无统计学意义（P>0.05）；微核试验在17.5~70.0 mg/kg剂量组的微核细胞率均<2.0‰，与溶剂对照组（1.2‰）比较，差异均无统计学意义（P>0.05）。结论： 小鼠、大鼠和Beagle犬对血清胸腺因子9肽的最大耐受剂量>70.0 mg/kg，按体质量计算相当于临床人拟用量的930倍；在本试验剂量范围内未见血清胸腺因子9肽的急性毒性和遗传毒性作用。

关键词: 血清胸腺因子9肽, 大鼠, 小鼠, Beagle犬, 急性毒性, 遗传毒性

Abstract: OBJECTIVE: To investigate acute toxicity and genotoxicity of an innovative antitumor drug -serum thymus factor 9 peptide. METHODS: Mice,rats,beagles were given 70.0 mg/kg by one-time injection to test for acute toxicity. Ames test,CHL test and micronucleus test were used to investigate genotoxicity. RESULTS: After treatments,the animals were in good spirits and behaved normally. There were no signs of excitation or inhibition. No acute toxicity was found. Ames test showed no significant increase in the number of mutant colonies at 1-5 000 μg/dish,similar to the solvent control group. CHL test showed no significant increase in chromosome aberration rate at 1 400-5 600 μg/mL (less than 3%),there was no statistical significance compared with the solvent control group (P>0.05). The micronucleus cell rates in the 17.5-70.0 mg/kg group were all less than 2.0‰,and there was no statistical significance compared with the solvent control group (1.2‰) (P>0.05). CONCLUSION: The maximum tolerated dose of serum thymic factor 9 peptide was greater than 70.0 mg/kg,which was 930 times of the recommended dosage for clinical patients. Acute toxicity and genotoxicity were not observed in the dose ranges for this investigation.

Key words: serum thymic factor 9 peptide, rats, mice, Beagles, acute toxicity, genotoxicity

中图分类号:

Q355

杨玉, 黄雅理, 林飞, 汤龙. 抗肿瘤血清胸腺因子9肽的急性毒性和遗传毒性[J]. 癌变·畸变·突变, 2022, 34(1): 57-61.

YANG Yu, HUANG Yali, LIN Fei, TANG Long. Acute toxicity and genotoxicity of antitumor serum thymic factor 9 peptide[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2022, 34(1): 57-61.

参考文献

[1] KOHDA Y, KAWAI Y, IWAMOTO N, et al. Serum thymic factor, FTS, attenuates cisplatin nephrotoxicity by suppressing cisplatin-induced ERK activation[J]. Biochem Pharmacol, 2005, 70(9):1408-1416.
[2] KOHDA Y, MATSUNAGA Y, YONOGI K, et al. Protective effect of serum thymic factor, FTS, on cephaloridine-induced nephrotoxicity in rats[J]. Biol Pharm Bull, 2005, 28(11):2087-2091.
[3] 张长平, 乐嘉静, 李湛君, 等. 血清胸腺因子(FTS)的抗肿瘤作用[J]. 药物分析杂志, 2007, 27(6):860-862.
[4] SEVERA M, ZHANG J, GIACOMINI E, et al. Thymosins in multiple sclerosis and its experimental models:moving from basic to clinical application[J]. Mult Scler Relat Disord, 2019, 27:52-60.
[5] 李湛军, 林飞, 范慧红, 等. 血清胸腺因子9肽对人结肠癌HT-29的抑瘤作用[J]. 癌变·畸变·突变, 2011, 23(5):374-376.
[6] 国家食品药品监督管理总局. 药物单次给药毒性研究技术指导原则[EB/OL]. (2014-05-13)[2021-05-06]. https://www.nmpa.gov.cn/xxgk/ggtg/qtggtg/20140513120001448.html.
[7] 国家食品药品监督管理总局. 药物遗传毒性研究技术指导原则[EB/OL]. (2018-03-15)[2021-05-06]. https://www.nmpa.gov.cn/directory/web/nmpa/xxgk/ggtg/qtggtg/20180315160901208.html.
[8] JUNG J A, NOH J H, JANG M S, et al. Safety evaluation of fermented Platycodon grandiflorus (Jacq.) A.DC. extract:genotoxicity, acute toxicity, and 13-week subchronic toxicity study in rats[J]. J Ethnopharmacol, 2021, 275:114138.
[9] CRISTINA DA COSTA ARALDI I, PIBER DE SOUZA T, DE SOUZA VENCATO M, et al. Preclinical safety assessment of the crude extract from Sida rhombifolia L. aerial parts in experimental models of acute and repeated-dose 28 days toxicity in rats[J]. Regul Toxicol Pharmacol, 2021, 124:104974.
[10] MERLINO P G, MARSH J A. The enhancement of avian NK cell cytotoxicity by thymulin is not mediated by the regulation of IFN-γ production[J]. Dev Comp Immunol, 2002, 26(1):103-110.
[11] YASUDA J, NISHIOKA W, SAKUDO A, et al. Suppressor mechanism of serum thymic factor on tumor necrosis factor-alpha-induced apoptosis in the mouse pancreatic beta-cell line[J]. Biochem Biophys Res Commun, 2003, 311(2):501-505.
[12] SAITOH N, AWAYA A, SAKUDO A, et al. Serum thymic factor prevents LPS-induced pancreatic cell damage in mice via up-regulation of bcl-2 expression in pancreas[J]. Microbiol Immunol, 2004, 48(9):629-638.
[13] LUNIN S M, NOVOSELOVA E G. Thymus hormones as prospective anti-inflammatory agents[J]. Expert Opin Ther Targets, 2010, 14(8):775-786.
[14] 郏建臣. 胸腺肽联合化疗对老年胃癌患者免疫功能及Th1、Th2细胞因子含量的影响[J]. 中国现代医学杂志, 2014, 24(36):51-54.
[15] 韩煦, 夏云龙. 抗肿瘤治疗相关的血管毒性[J]. 中国循环杂志, 2017, 32(7):716-718.
[16] 董超, 罗春香, 杨润祥. 抗肿瘤药物所致神经毒性防治的研究进展[J]. 重庆医学, 2018, 47(2):268-272.
[17] 孙星星, 闵大六. 抗肿瘤治疗所致心脏毒性的研究进展[J]. 中华诊断学电子杂志, 2019, 7(3):147-150.
[18] 陈素华, 刘红, 张艳华. 紫杉烷类抗肿瘤药物相关心血管毒性报告及文献分析[J]. 中国新药杂志, 2020, 29(20):2395-2400.

抗肿瘤血清胸腺因子9肽的急性毒性和遗传毒性

Acute toxicity and genotoxicity of antitumor serum thymic factor 9 peptide

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