Awogi T, Sato T
Department of Toxicology, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan.
Mutat Res. 1989 Aug;223(4):353-6. doi: 10.1016/0165-1218(89)90084-0.
The effect of route of administration on the outcome of the micronucleus test was examined by administering benzo[a]pyrene (B[a]P) perorally (p.o.) and intraperitoneally (i.p.) to males of the MS/Ae and CD-1 mouse strains. This study consisted of 3 parts. First, an acute toxicity study lasting 3 days was done to estimate LD50s. The LD50 was larger than 1600 mg/kg for both routes in the 2 strains. Second, pilot micronucleus tests were carried out, on the basis of which an appropriate sampling time (48 h) and dose levels (62.5, 125, 250, and 500 mg/kg) were chosen for both routes and both strains. Third, full-scale micronucleus tests were done, which indicated that (1) B[a]P induced micronuclei dose-dependently by each administration route in each strain, (2) the i.p. route induced frequencies of micronuclei almost equal to or slightly higher than did the p.o. route, and (3) the MS/Ae strain was the higher responder.
通过对MS/Ae和CD-1小鼠品系的雄性小鼠经口(p.o.)和腹腔内(i.p.)给予苯并[a]芘(B[a]P),研究了给药途径对微核试验结果的影响。本研究包括3个部分。首先,进行了一项为期3天的急性毒性研究以估计半数致死量(LD50)。在这两个品系中,两种给药途径的LD50均大于1600 mg/kg。其次,开展了预试验微核试验,在此基础上为两种给药途径和两个品系选择了合适的采样时间(48小时)和剂量水平(62.5、125、250和500 mg/kg)。第三,进行了全面的微核试验,结果表明:(1)在每个品系中,B[a]P通过每种给药途径均呈剂量依赖性地诱导微核形成;(2)腹腔内给药途径诱导的微核频率几乎等于或略高于经口给药途径;(3)MS/Ae品系是反应较高的品系。