中国新药杂志

非整倍体诱导剂的检测方法及风险评估

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赵田田 ¹ , 周长慧 ¹ , 王敬亭 ¹^,² , 杨紫轩 ¹ , 李嫚琪 ¹ , 常艳 ¹

中国新药杂志 | 重大新药创制专项巡礼 2021,30(6): 501-506

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中国新药杂志 |重大新药创制专项巡礼 2021 , 30 (6) : 501 -506

非整倍体诱导剂的检测方法及风险评估

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赵田田¹, 周长慧¹, 王敬亭¹^,², 杨紫轩¹, 李嫚琪¹, 常艳¹

作者信息

¹中国医药工业研究总院上海益诺思生物技术股份有限公司，上海　201203

²复旦大学药学院，上海　201203

通讯作者:

常艳，女，博士，研究员，主要从事药物毒理学研究。联系电话：（021）50800333-208，E-mail：ychang@innostar.cn。

作者简介:

赵田田，女，硕士研究生，主要从事遗传毒理学研究。E-mail：652369375@qq.com。

Progress in detection and risk assessment of aneugens

Tian-tian ZHAO¹, Chang-hui ZHOU¹, Jing-ting WANG¹^,², Zi-xuan YANG¹, Man-qi LI¹, Yan CHANG¹

Affiliations

¹China State Institute of Pharmaceutical Industry, National Shanghai Center for New Drug Safety Evaluation and Research/Shanghai InnoStar Bio-Tech Co., Ltd., Shanghai 201203, China

²School of Pharmacy, Fudan University, Shanghai 201203, China

出版时间: 2021-03-30

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摘要

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非整倍体（aneuploidy）指细胞核内染色体数不是染色体组的整倍数，包括单体、三体、四体、双三体、缺体等，与恶性肿瘤发生密切相关。非整倍体诱导剂（aneugen）指诱导子细胞染色体数目增加或减少，即导致非整倍体形成的物质。现行的遗传毒性试验指导原则要求评估化学物质诱发非整倍体的可能性，但标准的遗传毒性试验组合不包括专门评估非整倍体诱导剂的试验。微核试验结合FISH和CREST染色为染色体数目畸变提供了直接的证据；体外多终点试验和毒性追踪分析可通过MoA检测非整倍体诱导剂。目前对生殖细胞非整倍体诱导剂进行全面风险评估的数据较少，因此在未来有必要开展非整倍体诱导剂对生殖细胞影响的研究，并对其进行全面的风险评估，以补充这一领域数据的空缺。本文对目前哺乳动物体细胞和生殖细胞中非整倍体形成机制、检测方法、危害以及暴露后的风险评估进行综述。

关键词

非整倍体 / 非整倍体诱导剂 / 危害 / 检测方法 / 风险评估

Abstract

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Aneuploidy refers to the number of chromosomes in the nucleus that is not an integral multiple of genome, including monosomy, trisomy, tetrasomy, double trisomy, nullsomy, etc., and is closely related to cancer. An aneuge is a substance that induces increase or decrease in the number of chromosomes of daughter cells, that is, a substance that leads to the formation of aneuploidy. The current guidance on genotoxicity testing requires assessment of chemicals' potential to induce aneuploidy. However, the standard battery of genotoxicity does not include an independent test designed specially for aneuploidy test. Micronucleus assay with the staining of kinetochores and FISH provides direct evidence for chromosome or genome mutations. MultiFlow and ToxTracker assays provide mechanistic information and permit genotoxins to be distinguished based on their MoA. At present, there are few data on comprehensive risk assessment of aneugens in germ cells. Therefore, in the future, it is necessary to carry out research on the effect of aneugens on germ cells and conduct a comprehensive risk assessment to supplement the gaps of data in this field. This article reviewed the scientific literature on the biological mechanisms, methods used to detect chemical aneugens, risks of aneuploidy and ramifications of exposure to chemical aneugens for human health risk assessment.

Key words

aneuploidy / aneugens / hazard / detection / risk assessment

引用本文

赵田田, 周长慧, 王敬亭, 杨紫轩, 李嫚琪, 常艳. 非整倍体诱导剂的检测方法及风险评估. 中国新药杂志, 2021 , 30 (6) : 501 -506 .

Tian-tian ZHAO, Chang-hui ZHOU, Jing-ting WANG, Zi-xuan YANG, Man-qi LI, Yan CHANG. Progress in detection and risk assessment of aneugens[J]. Chinese Journal of New Drugs, 2021 , 30 (6) : 501 -506 .

基金

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国家“重大新药创制”科技重大专项资助项目(2018ZX09201017-008)
上海市科委研发公共服务平台项目(18DZ2290100)

参考文献

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2021年第30卷第6期

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首发时间：2026-10-29
出版时间：2021-03-30

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录用日期：2020-10-09

基金

国家“重大新药创制”科技重大专项资助项目(2018ZX09201017-008)

上海市科委研发公共服务平台项目(18DZ2290100)

作者信息

¹中国医药工业研究总院上海益诺思生物技术股份有限公司，上海　201203

²复旦大学药学院，上海　201203

通讯作者:

常艳，女，博士，研究员，主要从事药物毒理学研究。联系电话：（021）50800333-208，E-mail：ychang@innostar.cn。

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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