Carcinogenesis, Teratogenesis & Mutagenesis ›› 2016, Vol. 28 ›› Issue (6): 432-437.doi: 10.3969/j.issn.1004-616x.2016.06.004

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

YUAN Ye1,2, CHEN Dandan3, JING Shufang1,2, YU Yongsheng1,2, CHEN Jianheng4, WU Chunqi1,2, SHI Chang1,   

  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

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 14th 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 4th round of mating in the 250 mg/kg group. The average number of non-viable fetus decreased in the 6th 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

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