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Carcinogenic effects of different nitroso-compounds in Chinese hamsters. I. Dimethylnitrosamine and
Abstract:
Three hundred and twenty Chinese hamsters (Cricetulus griseus) (CH) were treated (s.c.) with 1/5, 1/10 or 1/20 LD50 of dimethylnitrosamine (DMN) or N-diethylnitrosamine (DEN). These substances, in several respects, showed a different organotropy in this species than in both the Syrian golden (SGH) and the European hamster (EH). In CH, DEN produced up to 100% squamous cell papillomata and occasionally also carcinomata of the cheek pouch, tongue, pharynix, oesophagus and forestomach. With DEN a high rate of hepatomata was simultaneously realized. DMN induced a considerable quantity of liver tumours, the highest incidence being demonstrated in the lowest dosage group.
Insights
Chinese hamsters treated with dimethylnitrosamine (DMN) and N-diethylnitrosamine (DEN) developed distinct tumors. DEN caused oral and esophageal cancers, while DMN primarily induced liver tumors, with lower doses showing higher incidence.
Area of Science:
- Toxicology
- Carcinogenesis
- Comparative Oncology
Background:
- Dimethylnitrosamine (DMN) and N-diethylnitrosamine (DEN) are known carcinogens.
- Species-specific differences in carcinogen metabolism and organotropism are crucial for understanding cancer development.
- Chinese hamsters (CH) represent a distinct rodent model for toxicological studies.
Purpose of the Study:
- To investigate the organ-specific toxicity and carcinogenicity of DMN and DEN in Chinese hamsters (CH).
- To compare the carcinogenic effects of DMN and DEN in CH with those observed in other hamster species, such as Syrian golden hamsters (SGH) and European hamsters (EH).
- To determine the dose-dependent effects of these nitrosamines on tumor induction in CH.
Main Methods:
- Three hundred and twenty Chinese hamsters were subcutaneously administered varying doses (1/5, 1/10, 1/20 LD50) of DMN or DEN.
- Tumor incidence and type were meticulously recorded across different organs.
- Comparative analysis was performed with existing data from SGH and EH models.
Main Results:
- N-diethylnitrosamine (DEN) induced a high incidence (up to 100%) of squamous cell papillomata and occasional carcinomata in the cheek pouch, tongue, pharynx, esophagus, and forestomach of CH.
- DEN also led to a significant rate of hepatomata (liver tumors) in Chinese hamsters.
- Dimethylnitrosamine (DMN) primarily induced a considerable quantity of liver tumors in CH, with the highest incidence observed in the lowest dosage group.
Conclusions:
- DMN and DEN exhibit different organotropic effects in Chinese hamsters compared to other hamster species.
- DEN is a potent carcinogen for the oral cavity, esophagus, and forestomach, and also induces liver tumors in CH.
- DMN is a potent hepatocarcinogen in CH, with a notable inverse dose-response relationship observed for tumor incidence.