Shelby M D, Witt K L
Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Environ Mol Mutagen. 1995;25(4):302-13. doi: 10.1002/em.2850250407.
Tests for the induction of chromosomal aberrations (ABS) and micronuclei (MN) in bone marrow cells of mice have been conducted on 65 chemicals. Although these tests were not conducted with the purpose of comparing the outcomes of these two in vivo genetic toxicity endpoints, the availability of these test results permits such a comparison. Based on studies to date, results from the 2 tests agree for more than 80% of the chemicals; 17 gave positive results in both tests, and 36 gave negative results in both. Seven chemicals were positive only for ABS and 5 were positive only for MN. Three chemicals that were originally concluded to be positive for ABS but not for MN were found to induce MN when the MN protocol was modified to more closely reflect the ABS protocol. Among the 12 chemicals for which there are discrepant results, there are only 2 for which the difference is convincing. One of these, selenium sulfide (MN negative, ABS positive) remains an enigma; further studies are being conducted. The second, isoprene (MN positive, ABS negative) will be difficult to pursue because the studies reported here were done by inhalation exposure. Based on the outcomes of these comparisons, protocol factors, rather than endpoint specificity, appear to be the major source of discrepant test results. Thus, these results do not support a recommendation that both tests be conducted in a primary testing scheme for genetic toxicity.
已对65种化学物质进行了小鼠骨髓细胞染色体畸变(ABS)和微核(MN)诱导试验。尽管进行这些试验并非为了比较这两个体内遗传毒性终点的结果,但这些试验结果的可得性使得能够进行这样的比较。根据迄今为止的研究,超过80%的化学物质在这两项试验中的结果一致;17种在两项试验中均呈阳性,36种在两项试验中均呈阴性。7种化学物质仅在ABS试验中呈阳性,5种仅在MN试验中呈阳性。当MN试验方案修改为更接近ABS试验方案时,发现最初被判定为ABS阳性但MN阴性的3种化学物质可诱导MN。在结果不一致的12种化学物质中,只有2种的差异具有说服力。其中一种,硫化硒(MN阴性,ABS阳性)仍然是个谜;正在进行进一步研究。第二种,异戊二烯(MN阳性,ABS阴性)将难以继续研究,因为此处报告的研究是通过吸入暴露进行的。基于这些比较的结果,试验方案因素而非终点特异性似乎是试验结果不一致的主要来源。因此,这些结果不支持在遗传毒性的初步试验方案中同时进行这两项试验的建议。