正丁基硫代磷酰三胺对体细胞和生殖细胞的致突变性研究

doi:10.3969/j.issn.1004-616x.2016.06.004

癌变·畸变·突变 ›› 2016, Vol. 28 ›› Issue (6): 432-437.doi: 10.3969/j.issn.1004-616x.2016.06.004

正丁基硫代磷酰三胺对体细胞和生殖细胞的致突变性研究

原野^1,2, 陈丹丹³, 荆淑芳^1,2, 于永生^1,2, 陈健恒⁴, 吴纯启^1,2, 施畅^1，

1. 军事医学科学院毒物药物研究所国家北京药物安全评价研究中心, 北京 100850;
2. 军事医学科学院抗毒药物与毒理学国家重点实验室, 北京 100850;
3. 中国食品药品检定研究院, 北京 100050;
4. YMS Agriculture International Corp., Toronto M5X 1C7, Ontario, Canada

收稿日期:2016-02-01 修回日期:2016-09-06 出版日期:2016-11-30 发布日期:2016-11-30
通讯作者: 施畅,E-mail:shichang1231@foxmail.com E-mail:shichang1231@foxmail.com
作者简介:原野,E-mail:13701181662@139.com。
基金资助:
重大新药创制科技重大专项基金（2013ZX09302303，2014ZX09507009-022）

Mutagenic effects of N-(n-butyl)-thiophosphorictriamide in somatic and germ cells of mice

YUAN Ye^1,2, CHEN Dandan³, JING Shufang^1,2, YU Yongsheng^1,2, CHEN Jianheng⁴, WU Chunqi^1,2, SHI Chang^1，

1. Beijing Institute of Pharmacology and Toxicology, National Beijing Center for Drug Safety Evaluation and Research, Beijing 100850;
2. State Key Laboratory of Toxicology and Medical Countermeasures, Academy of Military Medical Sciences, Beijing 100850;
3. National Institutes for Food and Drug Control, Beijing 100050, China;
4. YMS Agriculture International Corp., Toronto M5X 1C7, Ontario, Canada

Received:2016-02-01 Revised:2016-09-06 Online:2016-11-30 Published:2016-11-30

摘要/Abstract

摘要： 目的：采用小鼠骨髓细胞染色体畸变试验和小鼠显性致死突变试验评价正丁基硫代磷酰三胺（NBPT）对体细胞和生殖细胞的致突变性。方法：小鼠骨髓细胞染色体畸变试验中雄性小鼠分别单次灌胃给予NBPT 250、500、1 000 mg/kg，1 000 mg/kg组动物于给药后24、48及72 h取骨髓细胞制备骨髓片，其他组动物于给药后24 h取骨髓细胞制备骨髓片。每只动物在油镜下分析100个中期相骨髓细胞，记录染色体结构畸变、数目畸变和发生裂隙的细胞数。小鼠显性致死试验中雄鼠分别连续灌胃给予NBPT 250、500、1 000 mg/kg 5 d后，雌鼠与雄鼠同笼交配5 d，雄鼠再于2 d后与下一轮的雌鼠交配，共进行7个轮次的交配，每轮次1周，覆盖雄性小鼠整个生精周期。每轮次雌鼠于同笼结束后第14天处死，计数总着床数、黄体数、死胎、活胎和吸收胎数。结果：小鼠单次灌胃NBPT 24 h后，250、500、1 000 mg/kg剂量组骨髓细胞染色体结构畸变率分别为2.4%、3.0%和2.0%，1 000 mg/kg组24、48和72 h的骨髓细胞染色体结构畸变率均未超过4%，与溶媒对照组比较差异均无统计学意义（P>0.05）。各NBPT处理组染色体四倍体与裂隙的发生率也未出现与NBPT相关性的变化。小鼠显性致死试验的7个交配轮次中，NBPT 3个处理组受孕率为100%，母鼠平均着床数、黄体数、活胎数与溶媒对照组比较差异均无统计学意义（P>0.05）。仅在NBPT 250 mg/kg组发现第4交配轮次母鼠着床前丢失率增高，第6轮次母鼠窝均非活胎数降低，与溶媒对照组比较差异均有统计学意义（P<0.01）。NBPT 3个处理组各交配轮次母鼠的致死突变率大多为负值，偶见较低的正值。结论：在本试验条件下，NBPT无致小鼠骨髓细胞染色体畸变效应，对雄性ICR小鼠无显性致死突变作用。

关键词: 正丁基硫代磷酰三胺, 致突变性, 骨髓细胞染色体畸变试验, 显性致死试验

Abstract: OBJECTIVE: Mutagenic effects of N-(n-butyl)-thiophosphorictriamide (NBPT) in somatic and germ cells of adult male ICR mice were evaluated using the bone marrow chromosome aberration (CA) and dominant lethal mutation (DLM) assays. METHODS: In the CA assay,adult male ICR mice were exposed to NBPT at 250,500 and 1000 mg/kg by a single oral administration. For the 1 000 mg/kg group,bone marrow samples were harvested at 24,48 and 72 h after the treatment and slide were made. For the other groups,bone marrow samples were harvested at 24 h after the treatment. From slides of each mouse,100 metaphase bone marrow cells were observed for chromosome aberration, the cell numbers of chromosome aberration,polyploidy,gap were recorded respectively. In the DLM assay,after mice were exposed to NBPT for successive 5 days,each mated with 2 virgin females for 5 days at predetermined intervals (2 days) for a total 7 rounds. Females of each round were sacrificed on the 14^th day of pregnancy. The total number of implantation,number of corpora lutea,number of stillbirth,live births and fetal absorption were counted and recorded. RESULTS: Chromosome aberration rates for mice after 24 h of exposure to the three doses were 2.4%,3.0% and 2.0%,respectively. Chromosome aberration rates for the 1 000 mg/kg group were less than 4% after the 24,48 and 72 h of exposure. All the observed aberration rates were not significantly different from the vehicle control group (P>0.05). The incidence of tetraploid chromosome and gap for each group showed no correlation with NBPT treatment. In the DLM test,for the 7 batches of mating,pregnancy rates in three NBPT treated groups were 100%. In addition,the average number of maternal implantation,number of corpora lutea,number of live births showed no significant difference compared with the vehicle control group. Preimplantation loss rate increased only in the 4^th round of mating in the 250 mg/kg group. The average number of non-viable fetus decreased in the 6^th round of mating in the 250 mg/kg group. Both showed significant difference compared with the vehicle control (P<0.01). Lethal mutation rates for female mice for each mating round were mostly negative for all the exposed groups. CONCLUSION: Within our experimental conditions, NBPT did not induce bone marrow chromosome aberrations nor dominant lethal mutation.

Key words: N-(n-butyl)-thiophosphorictriamide, mutagenicity, bone marrow chromosome aberration test, dominant lethal mutation test

中图分类号:

R394.6
Q355

原野, 陈丹丹, 荆淑芳, 于永生, 陈健恒, 吴纯启, 施畅. 正丁基硫代磷酰三胺对体细胞和生殖细胞的致突变性研究[J]. 癌变·畸变·突变, 2016, 28(6): 432-437.

YUAN Ye, CHEN Dandan, JING Shufang, YU Yongsheng, CHEN Jianheng, WU Chunqi, SHI Chang. Mutagenic effects of N-(n-butyl)-thiophosphorictriamide in somatic and germ cells of mice[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2016, 28(6): 432-437.

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正丁基硫代磷酰三胺对体细胞和生殖细胞的致突变性研究

Mutagenic effects of N-(n-butyl)-thiophosphorictriamide in somatic and germ cells of mice

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