Ashby J, Mirkova E
Imperial Chemical Industries PLC, Central Toxicology Laboratory, Macclesfield, Cheshire, England.
Environ Mol Mutagen. 1987;10(3):297-305. doi: 10.1002/em.2850100308.
7,12-dimethylbenzanthracene (DMBA) is confirmed as active in the mouse bone marrow micronucleus assay 24 hr after dosing as a corn-oil homogenate via either oral gavage or intraperitoneal (ip) injection. These data are consistent with recent observations made by several investigators. However, when dosed via ip injection as a solution in DMSO, peak activity was evident 48 hr after dosing and a dramatic reduction in erythropoiesis was observed. The latter results are consistent with early observations made by Salamone and Heddle. The early observations of Salamone and Heddle were highlighted in the Gene-Tox review of this assay and led the OECD to recommend the use of 3 sampling times for this assay (between 12 and 72 hr). The present data indicate that this advice should be reviewed. In particular, it suggested that a maximum of two sampling times is adequate and that, as a consequence, the number of animals employed in the conduct of the test could be reduced with no loss of sensitivity. The present data also suggest that the use of a corn-oil homogenate of insoluble test agents may provide an efficient replacement for the use of ground suspensions or solutions in DMSO.
7,12 - 二甲基苯并蒽（DMBA）经证实，通过口服灌胃或腹腔注射作为玉米油匀浆给药后24小时，在小鼠骨髓微核试验中具有活性。这些数据与几位研究人员最近的观察结果一致。然而，当作为二甲基亚砜溶液通过腹腔注射给药时，给药后48小时活性达到峰值，并且观察到红细胞生成显著减少。后一结果与萨拉蒙内和赫德尔早期的观察结果一致。萨拉蒙内和赫德尔的早期观察结果在该试验的基因毒性综述中得到强调，并促使经合组织建议该试验采用3个采样时间（12至72小时之间）。目前的数据表明，这一建议应重新审视。特别是，研究表明最多两个采样时间就足够了，因此，进行试验所使用的动物数量可以减少，而不会降低敏感性。目前的数据还表明，使用不溶性受试物的玉米油匀浆可能为使用研磨悬浮液或二甲基亚砜溶液提供一种有效的替代方法。
