Hayashi M, Sofuni T, Kodama Y, Ishidate M, Tamura H
Division of Mutagenesis, National Institute of Hygienic Sciences, Tokyo, Japan.
Mutat Res. 1989 Aug;223(4):345-8. doi: 10.1016/0165-1218(89)90082-7.
The effect of route of administration on the outcome of the micronucleus test was evaluated in 2 laboratories by administering the model chemical, 1-beta-D-arabinofuranosylcytosine (Ara-C), by intraperitoneal injection (i.p.) and oral gavage (p.o.) to 2 mouse strains, MS/Ae and CD-1. On the basis of a small-scale acute toxicity study and a pilot experiment for the micronucleus test, a full-scale test was performed with a 24-h sampling time at doses of 12.5, 25, 50, and 100 mg/kg i.p. and 25, 50, 100, and 200 mg/kg p.o. In both strains, MNPCEs were induced at lower dose levels by the i.p. treatment, as determined not only on the basis of mg/kg but also as a ratio of the LD50. When compared with other chemicals tested in this collaborative study, the effective dose levels of this chemical based on the LD50s were exceptionally low by both routes and in both strains, e.g., less than 0.3% of the LD50 by the i.p. treatment. The maximum frequencies of MNPCEs induced were, however, identical (MS/Ae) or even higher (CD-1) by the p.o. treatment.
在2个实验室中，通过向MS/Ae和CD-1这2种小鼠品系腹腔注射（i.p.）和灌胃（p.o.）模型化学品1-β-D-阿拉伯呋喃糖基胞嘧啶（Ara-C），评估给药途径对微核试验结果的影响。基于小规模急性毒性研究和微核试验预试验，在给药后24小时取样，以12.5、25、50和100mg/kg腹腔注射以及25、50、100和200mg/kg灌胃的剂量进行了全面试验。在这两种品系中，腹腔注射处理在较低剂量水平即可诱导微核多染红细胞（MNPCEs），这不仅基于mg/kg来判断，还作为半数致死剂量（LD50）的比例来确定。与本协作研究中测试的其他化学品相比，该化学品基于LD50的有效剂量水平在两种给药途径和两种品系中都异常低，例如腹腔注射处理时低于LD50的0.3%。然而，灌胃处理诱导的MNPCEs的最大频率在MS/Ae品系中相同，在CD-1品系中甚至更高。
