Trzos R J, Petzold G L, Brunden M N, Swenberg J A
Mutat Res. 1978 Sep;58(1):79-86. doi: 10.1016/0165-1218(78)90097-6.
Sixteen carcinogens were evaluated in rats for their ability to induce micronuclei. The direct acting agent, ethyl methanesulfonate and the procarcinogens/promutagens, cyclophosphamide and 4-nitroquinoline-1-oxide, induced dose-related increases in micronucleated polychromatophilic erythrocytes. Aflatoxin B1 also significantly increased the number of micronucleated polychromatophillic erythrocytes for 2 doses although no dose-response could be detected. Dimethylnitrosamine produced variable results. The remaining 11 compounds, 2-acetylaminofluorene, 4-aminobiphenyl, benzidine, diethylnitrosamine, dimethylbenzanthracene, 1,2-dimethylhydrazine, ethionine, ethyl carbamate, hexametapol, metronidazole, and beta-naphthylamine, failed to induce significantly increased numbers of micronuclei. The large number of false negative results obtained in the present investigations using the micronucleus test suggests that in vivo cytogenetic assays utilizing bone marrow may also lack the sensitivity needed to detect clastogenic effects of procarcinogens/promutagens which require tissue specific metabolic activation.
在大鼠中评估了16种致癌物诱导微核的能力。直接作用剂甲磺酸乙酯以及前致癌物/促变剂环磷酰胺和4-硝基喹啉-1-氧化物，可诱导微核多染性红细胞数量呈剂量相关增加。黄曲霉毒素B1在两个剂量下也显著增加了微核多染性红细胞的数量，尽管未检测到剂量反应。二甲基亚硝胺产生了不同的结果。其余11种化合物，2-乙酰氨基芴、4-氨基联苯、联苯胺、二乙基亚硝胺、二甲基苯并蒽、1,2-二甲基肼、乙硫氨酸、氨基甲酸乙酯、偏磷酸六聚体、甲硝唑和β-萘胺，均未诱导微核数量显著增加。在本研究中使用微核试验获得的大量假阴性结果表明，利用骨髓进行的体内细胞遗传学检测也可能缺乏检测需要组织特异性代谢激活的前致癌物/促变剂的致断裂效应所需的敏感性。
