Ohuchida A, Furukawa A, Kondo Y, Ono T, Nito S
Drug Safety Laboratory, Taiho Pharmaceutical Co. Ltd., Tokushima, Japan.
Mutat Res. 1989 Aug;223(4):395-8. doi: 10.1016/0165-1218(89)90094-3.
The effects of vincristine sulfate (VINC) on micronucleus induction were studied in 2 strains of mice (MS/Ae: CD-1) following intraperitoneal (i.p.) or oral administration (p.o.) of the chemical. On the basis of a small-scale acute toxicity study and a pilot micronucleus experiment, the full-scale micronucleus test was performed with a sampling time of 24 h at doses of 0.063, 0.125, 0.25 and 0.5 mg/kg (i.p.) and 1.25, 2.5, 5.0 and 10 mg/kg (p.o.). The maximum frequency of micronucleated polychromatic erythrocytes was 7.15% in MS/Ae mice and 4.98% in CD-1 mice at 5.0 mg/kg p.o. in both cases. The maximum frequencies by the i.p. route (9.93% in MS/Ae mice; 11.68% in CD-1 mice) occurred at 0.25 mg/kg and 0.125 mg/kg, respectively. Although the doses showing a positive response were different between the 2 routes, VINC induced micronuclei very efficiently at all doses tested by both administration routes in both strains.
在2个品系的小鼠(MS/Ae:CD-1)中,研究了腹腔注射(i.p.)或口服(p.o.)硫酸长春新碱(VINC)对微核诱导的影响。基于小规模急性毒性研究和初步微核实验,在给药后24小时的采样时间,以0.063、0.125、0.25和0.5 mg/kg(腹腔注射)以及1.25、2.5、5.0和10 mg/kg(口服)的剂量进行了全面的微核试验。在两种情况下,口服5.0 mg/kg时,MS/Ae小鼠微核多染红细胞的最高频率为7.15%,CD-1小鼠为4.98%。腹腔注射途径的最高频率(MS/Ae小鼠为9.93%;CD-1小鼠为11.68%)分别出现在0.25 mg/kg和0.125 mg/kg。尽管两种途径显示阳性反应的剂量不同,但在两个品系中,VINC通过两种给药途径在所有测试剂量下都能非常有效地诱导微核。