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
发布时间：2018-07-29 10:59
【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(P0.05)。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(P0.05)。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(P0.01)。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。
[Abstract]:Aim: to evaluate the mutagenicity of normal Ding Ji phosphoryltriamine (NBPT) to somatic and germ cells by chromosome aberration test of bone marrow cells and dominant lethal mutation test in mice. Methods: in the chromosome aberration test of bone marrow cells in mice, male mice were given NBPT 250 500 mg / kg 1 000 mg/kg by single gavage, and bone marrow cells were taken from the mice at 24 h and 72 h after administration to prepare bone marrow slices. Bone marrow cells were taken from other groups 24 hours after administration. One hundred metaphase bone marrow cells were analyzed under oil microscope to record chromosomal structural aberration, number aberration and the number of cells with fissures. In the dominant lethal test of mice, male mice were fed with NBPT 250,500000 mg/kg for 5 days, female mice and male mice were mated in the same cage for 5 days, and male mice were mated with the next round of female mice 2 days later. Seven rounds of mating were carried out for one week each time. Covering the whole spermatogenic cycle of male mice. The female rats were killed on the 14th day after the same cage. The total number of implantation, the number of luteal bodies, the number of stillbirths, the number of live fetuses and the number of absorbed fetuses were counted. Results: the chromosomal structural aberration rate of bone marrow cells in NBPT group was 2.4% and 2.0000 mg/kg at 2448 and 72 h after single NBPT administration for 24 h. The results showed that the chromosome structural aberration rate of bone marrow cells in the dose group of 250,500,500 mg/kg was less than that of the control group, compared with that of the control group. The difference was not statistically significant (P0.05). The incidence of tetraploid and fissures of chromosomes in each NBPT treatment group was not correlated with NBPT. The pregnancy rate of NBPT treatment group was 100 in 7 mating cycles of dominant lethal test in mice. There was no significant difference in average implantation number, luteal body number, number of live fetus between NBPT treatment group and control group (P0.05). Only in the NBPT 250 mg/kg group, the rate of loss before implantation was increased, and the number of non-live embryos in the litter of the sixth round was decreased. Compared with the control group, the difference was statistically significant (P0.01). Conclusion: NBPT has no effect on chromosome aberration in bone marrow cells, but no dominant lethal mutation in male ICR mice.
【作者单位】： 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;军事医学科学院抗毒药物与毒理学国家重点实验室;中国食品药品检定研究院;YMS
【基金】：重大新药创制科技重大专项基金(2013ZX09302303,2014ZX095 07009-022)
【分类号】：R114
本文编号：2152467
[Abstract]:Aim: to evaluate the mutagenicity of normal Ding Ji phosphoryltriamine (NBPT) to somatic and germ cells by chromosome aberration test of bone marrow cells and dominant lethal mutation test in mice. Methods: in the chromosome aberration test of bone marrow cells in mice, male mice were given NBPT 250 500 mg / kg 1 000 mg/kg by single gavage, and bone marrow cells were taken from the mice at 24 h and 72 h after administration to prepare bone marrow slices. Bone marrow cells were taken from other groups 24 hours after administration. One hundred metaphase bone marrow cells were analyzed under oil microscope to record chromosomal structural aberration, number aberration and the number of cells with fissures. In the dominant lethal test of mice, male mice were fed with NBPT 250,500000 mg/kg for 5 days, female mice and male mice were mated in the same cage for 5 days, and male mice were mated with the next round of female mice 2 days later. Seven rounds of mating were carried out for one week each time. Covering the whole spermatogenic cycle of male mice. The female rats were killed on the 14th day after the same cage. The total number of implantation, the number of luteal bodies, the number of stillbirths, the number of live fetuses and the number of absorbed fetuses were counted. Results: the chromosomal structural aberration rate of bone marrow cells in NBPT group was 2.4% and 2.0000 mg/kg at 2448 and 72 h after single NBPT administration for 24 h. The results showed that the chromosome structural aberration rate of bone marrow cells in the dose group of 250,500,500 mg/kg was less than that of the control group, compared with that of the control group. The difference was not statistically significant (P0.05). The incidence of tetraploid and fissures of chromosomes in each NBPT treatment group was not correlated with NBPT. The pregnancy rate of NBPT treatment group was 100 in 7 mating cycles of dominant lethal test in mice. There was no significant difference in average implantation number, luteal body number, number of live fetus between NBPT treatment group and control group (P0.05). Only in the NBPT 250 mg/kg group, the rate of loss before implantation was increased, and the number of non-live embryos in the litter of the sixth round was decreased. Compared with the control group, the difference was statistically significant (P0.01). Conclusion: NBPT has no effect on chromosome aberration in bone marrow cells, but no dominant lethal mutation in male ICR mice.
【作者单位】： 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;军事医学科学院抗毒药物与毒理学国家重点实验室;中国食品药品检定研究院;YMS
【基金】：重大新药创制科技重大专项基金(2013ZX09302303,2014ZX095 07009-022)
【分类号】：R114
【相似文献】
相关期刊论文 前5条
1 侯慎行，，严文钰;2－氯－6－（三氯甲基）吡啶的显性致死试验[J];卫生毒理学杂志;1995年01期
2 何水淋;采用大鼠显性致死试验评价乙烯氧化物的潜在致突变性[J];国外医学参考资料(卫生学分册);1978年03期
3 侯召棠;用大鼠显性致死试验评价新鲜照射小麦的致突变性[J];国外医学(卫生学分册);1979年04期
4 王小芬,李厚永,张树来;二甲苯体内诱变试验研究[J];卫生毒理学杂志;1993年S1期
5 ;[J];;年期
本文编号：2152467
本文链接：https://www.wllwen.com/yixuelunwen/yufangyixuelunwen/2152467.html
