Nowak C, Gleier K, Christ M, Gorzelniak K, Richter-Reichhelm H B
Max-von-Pettenkofer Institut, Bundesgesundheitsamt, Berlin, Deutschland.
Exp Toxicol Pathol. 1993 May;45(2-3):81-6. doi: 10.1016/S0940-2993(11)80468-9.
Tracheas were excised from fetal Syrian golden hamsters on the 15th day of gestation. Tracheal explants were cultured in vitro and exposed to different dose-levels of well known carcinogens. We chose two nitroso compounds, N-Methyl-N-nitro-N-nitrosoguanidine (MNNG) and Diethylnitrosamine (DEN) and two aromatic amines, Aminofluorene (AF) and Acetylaminofluorene (AAF). The tracheal explants were treated for 24 h in vitro, then the carcinogens were washed off and the tracheas were kept for 21, 28 or 35 days in culture. After fixation tracheal explants were transversely cut with serial section techniques and scored for morphological changes of the epithelium by light microscopy. Most of the control explants completed differentiation and had a normal morphology at the end of the in vitro culture period. Occasionally we found a decrease of the number of ciliated cells and some areas with squamous metaplasia in the respiratory epithelium. Carcinogen treatment with nitroso compounds led to a significant increase of the morphologic changes of the epithelium. These effects were especially obvious after DEN treatment. Morphologic changes of the epithelium such as metaplasia and hyperplasia were discussed as carcinogen-related events. In vitro exposure with aromatic amines did not induce marked metaplastic or hyperplastic changes in the respiratory epithelium of tracheal explants.
在妊娠第15天从叙利亚金黄地鼠胎儿身上切除气管。将气管外植体进行体外培养,并暴露于不同剂量水平的知名致癌物中。我们选择了两种亚硝基化合物,N-甲基-N-硝基-N-亚硝基胍(MNNG)和二乙基亚硝胺(DEN),以及两种芳香胺,氨基芴(AF)和乙酰氨基芴(AAF)。气管外植体在体外处理24小时,然后洗去致癌物,将气管在培养中保存21、28或35天。固定后,采用连续切片技术对气管外植体进行横切,并通过光学显微镜对上皮细胞的形态变化进行评分。大多数对照外植体在体外培养期结束时完成分化并具有正常形态。偶尔我们会发现纤毛细胞数量减少,以及呼吸上皮中有一些鳞状化生区域。用亚硝基化合物进行致癌物处理导致上皮细胞形态变化显著增加。这些影响在DEN处理后尤其明显。上皮细胞的形态变化,如化生和增生,被认为是与致癌物相关的事件。气管外植体的呼吸上皮在体外暴露于芳香胺时未诱导明显的化生或增生变化。