Langenbach R, Leavitt S, Hix C, Sharief Y, Allen J W
Mutat Res. 1986 Jun;161(1):29-37. doi: 10.1016/0027-5107(86)90097-7.
Aminofluorene (AF) and dimethylnitrosamine (DMN) were examined for their ability to induce multiple genetic endpoints after rat and hamster hepatocyte metabolic activation. The endpoints measured included mutations at the Na+/K+-ATPase (ouabain resistance) and hypoxanthine-guanine-phosphoribosyltransferase (6-thioguanine resistance) loci, and sister-chromatid exchanges (SCEs) in Chinese hamster V79 cells, and mutation of Salmonella typhimurium strains TA98 and TA100. AF, with rat and hamster hepatocyte activation, induced only low levels of mutations at either loci in V79 cells but did induce SCEs. Mutation of Salmonella by AF after hepatocyte activation also occurred and was a sensitive endpoint for detecting this aromatic amine. DMN induced high levels of mutations at both loci in V79 cells in addition to SCEs in the presence of hepatocytes from both species. DMN was also mutagenic to Salmonella, but only with hamster hepatocytes. Salmonella did not respond as strongly to DMN as the V70 cells. Hamster hepatocytes were more active than rat hepatocytes in activating both carcinogens. The results indicate the variable sensitivity of the genetic endpoints and species differences in activation for two potent chemical carcinogens.
对氨基芴(AF)和二甲基亚硝胺(DMN)在大鼠和仓鼠肝细胞代谢活化后诱导多种遗传终点的能力进行了研究。所测量的终点包括钠钾ATP酶(哇巴因抗性)和次黄嘌呤-鸟嘌呤磷酸核糖转移酶(6-硫鸟嘌呤抗性)位点的突变、中国仓鼠V79细胞中的姐妹染色单体交换(SCE),以及鼠伤寒沙门氏菌TA98和TA100菌株的突变。经大鼠和仓鼠肝细胞活化后,AF仅在V79细胞的两个位点诱导低水平的突变,但确实诱导了SCE。肝细胞活化后AF对沙门氏菌的突变也会发生,并且是检测这种芳香胺的一个敏感终点。在两种物种的肝细胞存在的情况下,DMN除了诱导SCE外,还在V79细胞的两个位点诱导高水平的突变。DMN对沙门氏菌也具有致突变性,但仅在仓鼠肝细胞作用下。沙门氏菌对DMN的反应不如V70细胞强烈。仓鼠肝细胞在激活这两种致癌物方面比大鼠肝细胞更活跃。结果表明两种强效化学致癌物的遗传终点敏感性不同以及活化存在物种差异。