Vanparys P, Vermeiren F, Sysmans M, Temmerman R
Department of Toxicology, Janssen Pharmaceutica, Beerse, Belgium.
Mutat Res. 1990 Jun;244(2):95-103. doi: 10.1016/0165-7992(90)90056-p.
The aim of this work was to determine the usefulness of the micronucleus assay for the detection of aneugenic potential. Chemicals affecting microtubule assembly, i.e., colchicine, vinblastine sulfate and tubulazole, and chemicals affecting targets other than microtubuli, i.e., mitomycin C, cyclophosphamide and miconazole, and the clastogens azathioprine and procarbazine were administered once orally or intraperitoneally to male and female mice. Bone marrow preparations were made at 24, 48 and 72 h after dosing. All the clastogens and aneugens, except miconazole, yielded positive results in the micronucleus test. Measurements of the area of the micronuclei and their distribution clearly showed that the chemicals affecting microtubule assembly produced larger micronuclei than did the clastogens. The pattern of area distribution of the micronuclei found with cyclophosphamide and mitomycin C was between those found for the tubulin inhibitors and the clastogens. These findings indicate that the micronucleus test not only detects chemicals affecting microtubule assembly, but also can discriminate them from clastogens by measurements of the area of the micronuclei.
本研究的目的是确定微核试验在检测非整倍体诱导潜力方面的实用性。对雄性和雌性小鼠口服或腹腔注射一次影响微管组装的化学物质,即秋水仙碱、硫酸长春碱和微管唑,以及影响微管以外靶点的化学物质,即丝裂霉素C、环磷酰胺和咪康唑,还有断裂剂硫唑嘌呤和丙卡巴肼。给药后24、48和72小时制备骨髓标本。除咪康唑外,所有断裂剂和非整倍体诱导剂在微核试验中均产生阳性结果。微核面积及其分布的测量清楚地表明,影响微管组装的化学物质产生的微核比断裂剂产生的微核更大。环磷酰胺和丝裂霉素C的微核面积分布模式介于微管蛋白抑制剂和断裂剂之间。这些发现表明,微核试验不仅能检测影响微管组装的化学物质,还能通过测量微核面积将它们与断裂剂区分开来。