Krishna G, Theiss J C
Department of Pathology and Experimental Toxicology, Parke-Davis Pharmaceutical Research, Ann Arbor, MI 48105, USA.
Environ Mol Mutagen. 1995;25(4):314-20. doi: 10.1002/em.2850250408.
Simultaneous assessment of in vivo micronucleus and chromosome aberration endpoints has been described in the rat and the mouse. Bone marrow and spleen cells were utilized for genotoxicity assessment. A cellulose column methodology was used in the micronucleus assay (where applicable) to eliminate nucleated cells and facilitate cytogenetic scoring. The test agents--cyclophosphamide, chlorambucil, and acrylamide--produced qualitatively comparable results between micronucleus and chromosome aberration endpoints and varied slightly on a quantitative basis depending on the type of test agent and tissue studied. The results from test agents such as cyclophosphamide, chlorambucil, acrylamide, dimethylnitrosamine, vincristine, and x-rays indicated that bone marrow cytogenetic results are similar to spleen and that the spleen tissue is at least as sensitive as the bone marrow. The concurrent analysis of cytogenetic damage in vivo using a multiple endpoint-multiple tissue approach described here has the following advantages: a) reducing the overall animal usage, b) clarifying marginal micronucleus and/or chromosome aberration data, c) correlating cytogenetic results from multiple endpoints and multiple tissues, and d) helping the investigation of the mechanism of action of test agents and their potential target organs. Also, the multiple endpoint-multiple tissue approach can be extended to other endpoints, tissues, and species (where appropriate and practical) to obtain detailed genotoxicity information.
在大鼠和小鼠中已描述了对体内微核和染色体畸变终点的同时评估。骨髓和脾细胞用于遗传毒性评估。在微核试验（如适用）中使用纤维素柱方法来去除有核细胞并便于细胞遗传学评分。测试剂——环磷酰胺、苯丁酸氮芥和丙烯酰胺——在微核和染色体畸变终点之间产生了定性可比的结果，并且根据测试剂类型和所研究组织的不同在定量上略有差异。来自环磷酰胺、苯丁酸氮芥、丙烯酰胺、二甲基亚硝胺、长春新碱和X射线等测试剂的结果表明，骨髓细胞遗传学结果与脾相似，并且脾组织至少与骨髓一样敏感。使用本文所述的多终点-多组织方法对体内细胞遗传损伤进行同时分析具有以下优点：a）减少整体动物使用量，b）澄清边缘微核和/或染色体畸变数据，c）关联多个终点和多个组织的细胞遗传学结果，以及d）有助于研究测试剂的作用机制及其潜在靶器官。此外，多终点-多组织方法可以扩展到其他终点、组织和物种（在适当且可行的情况下）以获得详细的遗传毒性信息。
