Hayashi M, Sutou S, Shimada H, Sato S, Sasaki Y F, Wakata A
Division of Mutagenesis, National Institute of Hygienic Sciences, Tokyo, Japan.
Mutat Res. 1989 Aug;223(4):329-44. doi: 10.1016/0165-1218(89)90081-5.
In the third collaborative study organized by the Collaborative Study Group for the Micronucleus Test (CSGMT), a task group belonging to the Mammalian Mutagenesis Study subgroup of the Environmental Mutagen Society of Japan (JEMS.MMS), intraperitoneal (i.p.) injection and oral (p.o.) gavage were compared as routes of administration of test chemicals. Two mouse strains, MS/Ae and CD-1, and 17 chemicals with various modes of action were used. The chemicals were 1-beta-D-arabinofuranosylcytosine, 6-mercaptopurine monohydrate, benzo[a]pyrene, 7,12-dimethylbenz[a]anthracene, 2-acetylaminofluorene, phenacetin, cyclophosphamide, ethyl methanesulfonate, N-ethyl-N-nitrosourea, methyl methanesulfonate, mitomycin C, colchicine, vincristine sulfate, potassium bromate, potassium chromate(VI), benzene, and procarbazine hydrochloride. On the basis of the findings of an acute toxicity test and a pilot experiment for dose and sampling time, a full-scale micronucleus test was performed on each chemical. Almost all the chemicals showed a positive response in micronucleus induction by both routes of administration in both mouse strains. Contradictory outcomes were obtained between the i.p. and p.o. routes on potassium chromate in both strains (i.p.: positive, p.o.: negative). In the CD-1 mice, benzene potently induced micronuclei when administered p.o., but gave only a marginal response when administered i.p. Generally, the chemicals induced micronuclei at lower dose levels (mg/kg) when administered i.p. This tendency, however, was decreased or even reversed when the dose was expressed as a percentage of the LD50. Although the i.p. route, an artificial exposure route, is useful to detect the inducibility of micronuclei of a test chemical per se at a small dose, the p.o. route seemed sensitive and valuable enough to evaluate the test chemicals. When the dose levels of chemicals are adjusted on the basis of the LD50, both i.p. injection and p.o. gavage are acceptable as routes of administration in the micronucleus test.
在微核试验协作研究组（CSGMT）组织的第三次协作研究中，一个隶属于日本环境诱变剂学会哺乳动物诱变研究亚组（JEMS.MMS）的任务组，对腹腔注射（i.p.）和灌胃（p.o.）作为受试化学物给药途径进行了比较。使用了两种小鼠品系，MS/Ae和CD - 1，以及17种具有不同作用方式的化学物。这些化学物分别是1 - β - D - 阿拉伯呋喃糖基胞嘧啶、一水合6 - 巯基嘌呤、苯并[a]芘、7,12 - 二甲基苯并[a]蒽、2 - 乙酰氨基芴、非那西丁、环磷酰胺、甲磺酸乙酯、N - 乙基 - N - 亚硝基脲、甲磺酸甲酯、丝裂霉素C、秋水仙碱、硫酸长春新碱、溴酸钾、铬（VI）酸钾、苯和盐酸丙卡巴肼。根据急性毒性试验以及剂量和采样时间预试验的结果，对每种化学物进行了全面的微核试验。几乎所有化学物在两种小鼠品系中通过两种给药途径都显示出微核诱导的阳性反应。两种品系中铬（VI）酸钾在腹腔注射和灌胃途径之间得到了相互矛盾的结果（腹腔注射：阳性，灌胃：阴性）。 在CD - 1小鼠中，苯经灌胃给药时能有效诱导微核，但腹腔注射时仅产生微弱反应。一般来说，化学物经腹腔注射给药时在较低剂量水平（mg/kg）就能诱导微核。然而，当剂量以LD50的百分比表示时，这种趋势会减弱甚至逆转。尽管腹腔注射途径是一种人为暴露途径，对于在小剂量下检测受试化学物本身的微核诱导能力很有用，但灌胃途径似乎足够灵敏且有价值来评估受试化学物。当根据LD50调整化学物的剂量水平时，腹腔注射和灌胃作为微核试验的给药途径都是可以接受的。
