Galloway S M
Merck Research Laboratories, West Point, PA 19486, USA.
Mutat Res. 1996 Jun 10;352(1-2):185-8. doi: 10.1016/0027-5107(95)00225-1.
In the study by Shelby et al. (1993) on 49 chemicals, the results of the micronucleus (MN) test in mouse bone marrow were compared with the results of the 2 year rodent carcinogenicity assays. Seven of the 25 rodent carcinogens were considered positive in the MN test, 5 following a protocol in which chemicals were given in three daily doses, and a further 2 when the chemical was administered only once. This low rate of positive results has led to disappointment in the MN test as a screen for carcinogens, but a careful examination of the data and of its analysis by Shelby et al. (1993) shows that many of the negative results are appropriate because: of the 18 carcinogens that were negative in the MN test, 1 has been retested and found to be non-carcinogenic, 9 were non-genotoxic and at least 2 were site-of-contact carcinogens not expected to be detected in the bone marrow. Two others were clearly positive in the MN test in other labs. Thus, the MN test 'missed' not 18 carcinogens, but 4 genotoxic carcinogens. The significance of these 4 needs further assessment, since three were liver specific carcinogens and the fourth was a very weak inducer of hemangiosarcomas in female mice only. Overall, the results of Shelby et al. (1993) do not cast such a shadow on the micronucleus test as many feared, and must be examined in the context of all the information available on each chemical. As Ashby and Tinwell emphasize in the accompanying article and in Tinwell and Ashby (1994), the data show that the MN test is capable of identifying human carcinogens and rodent germ cell mutagens, and remains a useful part of genotoxicity evaluation of chemicals.
在谢尔比等人（1993年）对49种化学物质的研究中，将小鼠骨髓微核（MN）试验的结果与两年期啮齿动物致癌性试验的结果进行了比较。25种啮齿动物致癌物中有7种在MN试验中被判定为阳性，其中5种是按照化学品每日分三次给药的方案进行试验的，另外2种是仅给药一次的情况下判定为阳性的。如此低的阳性率使得人们对MN试验作为致癌物筛选方法感到失望，但是仔细审查谢尔比等人（1993年）的数据及其分析可以发现，许多阴性结果是合理的，原因如下：在MN试验中呈阴性的18种致癌物中，1种经过重新检测后发现无致癌性，9种无基因毒性，至少2种是接触部位致癌物，预计在骨髓中无法检测到。另外两种在其他实验室的MN试验中明显呈阳性。因此，MN试验“遗漏”的不是这18种致癌物，而是4种基因毒性致癌物。这4种致癌物的意义需要进一步评估，因为其中3种是肝脏特异性致癌物，第4种仅在雌性小鼠中是血管肉瘤的非常弱的诱导剂。总体而言，谢尔比等人（1993年）的结果并没有像许多人担心的那样给微核试验蒙上阴影，必须结合每种化学物质的所有现有信息来审视这些结果。正如阿什比和廷韦尔在随附文章以及廷韦尔和阿什比（1994年）中所强调的，数据表明MN试验能够识别人类致癌物和啮齿动物生殖细胞诱变剂，并且仍然是化学品遗传毒性评估的一个有用部分。
