Massa T, Esmaeili A, Fortmeyer H, Schlatterer B, Hagenmaier H, Chandra P
Laboratorium für Molekularbiologie (ZBC), Klinikum der Johann-Wolfgang Goethe Universität, Frankfurt/Main, Germany.
Anticancer Res. 1992 Nov-Dec;12(6B):2053-60.
We have developed a host-mediated assay system for detection of the transforming activity of chemical carcinogens on peritoneal macrophages, directly, as well as indirectly acting carcinogenic substances administered intraperitoneally to NMRI mice could be examined in this way. Resident macrophages were recovered by peritoneal lavage from treated and untreated mice and cultured in soft agar. After 5-6 days normal and transformed cells could be distinguished. Statistical analysis comparing cells from 2, 3, 7, 8-tetrachlorodibenzo-dioxin (TCDD)-treated animals with those from control mice proved that the test is positive at least on a significance level of 5%, using the t-test. TCDD revealed a cell-transforming potential that showed a dose-dependent response in this host-mediated assay. The co-carcinogenic activity of TCDD was established in experiments with diphenylhydantoin. Low doses of diphenylhydantoin which did not exhibit any transforming potential in our system gained a high oncogenic potential by the simultaneous administration of low doses of TCDD, which also had no transforming activity. We have compared the cell transforming potential of TCDD with its bromo analog TBrDD. The cell transforming potential of TCDD is 7 times that of TBrDD. We have succeeded in establishing a permanent cell lined from mice treated with TBrDD. The oncogenicity of this cell line was tested in athymic nu/nu mice. Animals treated subcutaneously with these cells (1 x 10(6) cells) developed tumors at the injection site. Using monospecific antibodies to tumor necrosis factor alpha (TNF-alpha), we have found that TCDD stimulates the secretion of TNF-alpha. The experimental data reported here lead to the conclusion that TCDD has a carcinogenic as well as a co-carcinogenic activity and has the property to induce TNF-alpha.
我们开发了一种宿主介导的检测系统，用于直接检测化学致癌物对腹膜巨噬细胞的转化活性，通过这种方式可以检测腹腔注射给NMRI小鼠的直接和间接作用的致癌物质。通过腹腔灌洗从处理过和未处理过的小鼠中回收驻留巨噬细胞，并在软琼脂中培养。5-6天后，可以区分正常细胞和转化细胞。使用t检验对来自2,3,7,8-四氯二苯并二恶英（TCDD）处理动物的细胞与对照小鼠的细胞进行统计分析，结果证明该检测至少在5%的显著性水平上呈阳性。在这种宿主介导的检测中，TCDD显示出细胞转化潜力，并呈现剂量依赖性反应。在与苯妥英的实验中确定了TCDD的促癌活性。在我们的系统中未表现出任何转化潜力的低剂量苯妥英，通过同时给予同样没有转化活性的低剂量TCDD，获得了高致癌潜力。我们比较了TCDD与其溴代类似物TBrDD的细胞转化潜力。TCDD的细胞转化潜力是TBrDD的7倍。我们成功地从用TBrDD处理的小鼠中建立了一个永久细胞系。在无胸腺裸鼠中测试了该细胞系的致癌性。用这些细胞（1×10⁶个细胞）皮下处理的动物在注射部位出现了肿瘤。使用针对肿瘤坏死因子α（TNF-α）的单特异性抗体，我们发现TCDD刺激TNF-α的分泌。这里报道的实验数据得出结论，TCDD具有致癌和促癌活性，并且具有诱导TNF-α的特性。
