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Carcinogenic effect of nitrosoalkylureas and nitrosoalkylcarbamates in Syrian hamsters
Abstract:
Three nitrosoalkylureas, two nitrosotrialkylureas, and three nitrosoalkylcarbamates were given to Syrian golden hamsters by gavage at approximately equimolar doses. Measured by the time to death with tumors as an index, nitrosoethylurea was the most potent carcinogen, followed by nitroso-2-hydroxyethylurea, which was less effective in males than in females. The least effective compounds, by this measure, were nitrosooxazolidone and nitroso-5-methyloxazolidone. The remaining compounds, nitroso-N-ethylurethan, nitroso-2-hydroxypropylurea, nitrosomethyldiethylurea, and nitrosotriethylurea appeared to be of similar potency. All of the compounds induced papillomas or carcinomas of the nonglandular stomach in high incidence, except in the groups given nitrosohydroxyethylurea or nitrosooxazolidone; exceptionally, only 35% of the latter group had tumors, compared with 70% or more in the other groups. All of the nitrosoalkylureas induced a high incidence of hemangiosarcomas of the spleen, but the nitrosoalkylcarbamates did not. The quite uniform response of the hamster to these compounds contrasts with the great variety of organs and cell types in which they induce tumors in the rat.
Insights
Nitrosoethylurea is a potent carcinogen in hamsters, causing stomach tumors and spleen hemangiosarcomas. Different nitroso compounds show varying potencies and tumor types, unlike in rats.
Area of Science:
- Toxicology
- Carcinogenesis
- Oncology
Background:
- Nitrosoalkylureas and related compounds are known carcinogens.
- Rodent models are crucial for understanding chemical carcinogenesis.
- Species-specific responses to carcinogens highlight the complexity of cancer development.
Purpose of the Study:
- To compare the carcinogenic potency of various nitroso compounds in Syrian golden hamsters.
- To investigate the spectrum of tumors induced by these agents.
- To assess species-specific differences in carcinogenicity compared to rats.
Main Methods:
- Administration of equimolar doses of nine nitroso compounds (nitrosoalkylureas, nitrosotrialkylureas, nitrosoalkylcarbamates) via gavage to Syrian golden hamsters.
- Monitoring survival time and tumor incidence as measures of carcinogenicity.
- Histopathological examination to identify tumor types and locations.
Main Results:
- Nitrosoethylurea was the most potent carcinogen; nitroso-2-hydroxyethylurea showed sex-specific differences in efficacy.
- All compounds induced high incidences of nonglandular stomach tumors, except for nitrosohydroxyethylurea and nitrosooxazolidone.
- Nitrosoalkylureas induced splenic hemangiosarcomas, whereas nitrosoalkylcarbamates did not.
Conclusions:
- Syrian golden hamsters exhibit a relatively uniform tumor response to these nitroso compounds.
- The hamster model provides a distinct profile of carcinogenicity compared to the rat model.
- These findings contribute to understanding structure-activity relationships in chemical carcinogenesis.