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Effects of nitroso compounds and aromatic amines on fetal tracheal explants
1Max-von-Pettenkofer Institut, Bundesgesundheitsamt, Berlin, Deutschland.
Abstract:
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.
Insights
Nitroso compounds like DEN significantly altered hamster tracheal explants, causing metaplasia and hyperplasia. Aromatic amines did not induce these significant morphological changes in the respiratory epithelium.
Area of Science:
- Toxicology
- Carcinogenesis
- Respiratory Medicine
Background:
- In vitro models are crucial for studying chemical carcinogen effects on respiratory tissues.
- Understanding epithelial changes in the trachea is vital for assessing carcinogen risk.
Purpose of the Study:
- To investigate the in vitro effects of specific nitroso compounds and aromatic amines on fetal Syrian golden hamster tracheal explants.
- To evaluate carcinogen-induced morphological alterations in the tracheal epithelium.
Main Methods:
- Fetal hamster tracheas were cultured in vitro and exposed to N-Methyl-N-nitro-N-nitrosoguanidine (MNNG), Diethylnitrosamine (DEN), Aminofluorene (AF), and Acetylaminofluorene (AAF).
- Explants were cultured for 21-35 days post-exposure, then sectioned and examined for epithelial morphology via light microscopy.
Main Results:
- Nitroso compounds, particularly DEN, significantly increased metaplasia and hyperplasia in the tracheal epithelium.
- Aromatic amines (AF, AAF) did not induce significant metaplastic or hyperplastic changes.
- Control explants generally showed normal differentiation, with occasional ciliary cell reduction or squamous metaplasia.
Conclusions:
- Nitroso compounds are potent inducers of morphological changes in respiratory epithelium in vitro.
- Diethylnitrosamine (DEN) demonstrates significant carcinogenic potential in this tracheal organ culture model.
- Aromatic amines showed limited capacity to induce metaplasia or hyperplasia under these experimental conditions.