Sutou S, Sato S, Hitotsumachi S, Kimura Y
Central Research Institute, Itoham Foods Inc., Tokyo, Japan.
Mutat Res. 1989 Aug;223(4):377-81. doi: 10.1016/0165-1218(89)90090-6.
Administration-route-related differences in the micronucleus test were examined by giving N-ethyl-N-nitrosourea (ENU) to male mice of the MS/Ae and CD-1 strains by 2 different routes, intraperitoneally (i.p.) and orally (p.o.). The experiments consisted of 3 parts: (1) a simplified acute toxicity study, which gave LD50s of 490 (i.p.) and 840 mg/kg (p.o.) in MS/Ae and 640 (i.p.) and 960 mg/kg (p.o.) in CD-1 mice: (2) a pilot experiment for the full-scale micronucleus test to determine appropriate dosages and sampling time: and (3) the micronucleus test at doses of 12.5, 25, 50, and 100 mg/kg with a sampling time of 24 h. The results indicated that no route-related differences existed at the 2 lowest doses. At 50 mg/kg, markedly higher numbers of micronucleated polychromatic erythrocytes (MNPCEs) were induced in both mouse strains by the i.p. route. At 100 mg/kg, the difference between the routes decreased in strain CD-1 and even reversed in MS/Ae. Thus, route-related differences appeared to depend on the dose. Such differences became small, however, in both strains when the comparison was made on the basis of LD50 values.
通过腹腔注射（i.p.）和口服（p.o.）两种不同途径给MS/Ae和CD-1品系的雄性小鼠施用N-乙基-N-亚硝基脲（ENU），研究了微核试验中给药途径相关的差异。实验包括三个部分：（1）简化的急性毒性研究，MS/Ae小鼠腹腔注射的半数致死量（LD50）为490mg/kg，口服为840mg/kg；CD-1小鼠腹腔注射为640mg/kg，口服为960mg/kg；（2）大规模微核试验的预试验，以确定合适的剂量和取样时间；（3）剂量为12.5、25、50和100mg/kg且取样时间为24小时的微核试验。结果表明，在两个最低剂量下不存在给药途径相关的差异。在50mg/kg时，腹腔注射途径在两个小鼠品系中均诱导出明显更多的微核多染红细胞（MNPCEs）。在100mg/kg时，CD-1品系中给药途径之间的差异减小，在MS/Ae品系中甚至逆转。因此，给药途径相关的差异似乎取决于剂量。然而，当基于LD50值进行比较时，两个品系中的这种差异都变小了。
