Vanparys P, Deknudt G, Vermeiren F, Sysmans M, Marsboom R
Department of Toxicology, Janssen Pharmaceutica, Beerse, Belgium.
Mutat Res. 1992 Jul;282(3):191-6. doi: 10.1016/0165-7992(92)90094-x.
A series of micronucleus inducers were evaluated in the mouse bone marrow micronucleus test to determine if a 72-h sampling time enhances the sensitivity for detecting genotoxic agents. Male and female Swiss albino mice were dosed once with 7,12- dimethylbenz[a]anthracene, 6-mercaptopurine, benzo[a]pyrene, benzene, cyclophosphamide, 2-acetylaminofluorene, tubulazole, or mitomycin C. According to the EEC and OECD guidelines, the mice were killed at 24, 48 and 72 h after dosing. All test compounds induced an increase in the number of micronucleated polychromatic erythrocytes at 24 and/or 48 h. From the results obtained, it was evident that the 72-h sampling time does not enhance the sensitivity of the micronucleus test. The present data show that for screening purposes two sampling times at 24 and 48 h are sufficient to detect clastogens as well as aneugens. Although quantitative differences were found in sensitivity to micronucleus inducers between male and female mice, no qualitative differences were observed between the two sexes.
在小鼠骨髓微核试验中评估了一系列微核诱导剂,以确定72小时的采样时间是否能提高检测遗传毒性剂的敏感性。雄性和雌性瑞士白化小鼠单次给予7,12-二甲基苯并[a]蒽、6-巯基嘌呤、苯并[a]芘、苯、环磷酰胺、2-乙酰氨基芴、tubulazole或丝裂霉素C。根据欧洲经济共同体和经济合作与发展组织的指南,在给药后24、48和72小时处死小鼠。所有受试化合物在24小时和/或48小时均诱导微核多染性红细胞数量增加。从获得的结果来看,很明显72小时的采样时间并不能提高微核试验的敏感性。目前的数据表明,出于筛选目的,24小时和48小时的两个采样时间足以检测断裂剂和非整倍体剂。虽然在雄性和雌性小鼠对微核诱导剂的敏感性上发现了定量差异,但在两性之间未观察到定性差异。