Wakata A, Yamashita T, Tamaoki M, Ohshima T, Kojima M
Safety Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd., Tokyo, Japan.
Mutat Res. 1989 Aug;223(4):369-72. doi: 10.1016/0165-1218(89)90088-8.
The effect of route of administration on the micronucleus test was examined in 2 laboratories: cyclophosphamide (CYP) was administered by intraperitoneal injection (i.p.) or oral gavage (p.o.) to 2 strains of mice. MS/Ae and CD-1. On the basis of a small-scale acute toxicity study and a pilot micronucleus experiment, the final micronucleus test was performed with a 48-h sampling time at doses of 25-200 mg/kg i.p. and 50-400 mg/kg p.o. CYP via the i.p. route was more toxic and induced more micronucleated polychromatic erythrocytes (MNPCEs) in MS/Ae mice than in CD-1 mice. Administration-route-related differences were not distinctly shown in the MS/Ae strain. In CD-1, however, higher doses were required for the p.o. route than for the i.p. route to induce about equal amounts of clastogenic damage.
在2个实验室研究了给药途径对微核试验的影响:将环磷酰胺(CYP)通过腹腔注射(i.p.)或灌胃(p.o.)给予2个品系的小鼠,即MS/Ae和CD-1。基于小规模急性毒性研究和初步微核试验,最终微核试验在48小时采样时间下进行,腹腔注射剂量为25-200mg/kg,灌胃剂量为50-400mg/kg。与灌胃途径相比,腹腔注射途径的CYP对MS/Ae小鼠毒性更大,诱导产生的微核多染红细胞(MNPCEs)更多。在MS/Ae品系中未明显显示出给药途径相关差异。然而,在CD-1品系中,灌胃途径诱导同等程度的致断裂损伤所需剂量高于腹腔注射途径。