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Carcinogenesis in rats by asymmetric nitrosamines containing an allyl group
Abstract:
Four asymmetric nitrosamines containing 1 allyl group were administered to rats in drinking water to aid in understanding the failure of nitrosodiallylamine ( NDAA ) to induce tumors in rats. Three of the compounds were given at equimolar doses, the fourth at somewhat lower dose. All four nitrosamines induced tumors of the esophagus and/or nasal cavity. Nitrosoallylethanolamine (NAE) induced a 30% incidence of hepatocellular carcinomas, while nitrosoallyl -2- hydroxypropylamine induced 70% hepatocellular carcinomas and a much lower dose of nitrosoallyl -2- oxopropylamine induced 80% of hepatocellular carcinomas, several of which metastasized. Nitrosoallyl -2,3- dihydroxypropylamine , which increased the mortality from tumors much more than the other compounds, failed to induce tumors in the liver, but induced a high incidence (85%) of tumors of the esophagus. The conclusion is that the allyl group is not metabolically inert, but that its presence in these molecules modifies their metabolism so as to give rise to tumors in a variety of organs. It does not seem that formation of an allylating agent is the common mechanism of carcinogenesis by these compounds.
Insights
The presence of an allyl group in nitrosamines modifies their metabolism, leading to tumors in various organs like the esophagus and liver in rats. This study clarifies the carcinogenic potential of these compounds.
Area of Science:
- Toxicology
- Carcinogenesis Research
- Organic Chemistry
Background:
- Nitrosodiallylamine (NDAA) failed to induce tumors in rats, prompting further investigation into related compounds.
- Understanding the metabolic fate and carcinogenic mechanisms of nitrosamines is crucial for risk assessment.
Purpose of the Study:
- To investigate the carcinogenic effects of four asymmetric nitrosamines containing an allyl group in rats.
- To elucidate the role of the allyl group in the metabolism and tumor induction of nitrosamines.
Main Methods:
- Administration of four distinct allyl-containing nitrosamines to rats via drinking water at equimolar or lower doses.
- Monitoring tumor incidence in various organs, including the esophagus, nasal cavity, and liver.
Main Results:
- All tested nitrosamines induced tumors in the esophagus and/or nasal cavity.
- Hepatocellular carcinomas were observed with nitrosoallylethanolamine (30%), nitrosoallyl-2-hydroxypropylamine (70%), and nitrosoallyl-2-oxopropylamine (80%, with metastasis).
- Nitrosoallyl-2,3-dihydroxypropylamine induced a high incidence of esophageal tumors (85%) but not liver tumors.
Conclusions:
- The allyl group is metabolically active and influences the organ-specific carcinogenicity of nitrosamines.
- The mechanism of carcinogenesis for these compounds likely does not involve a common allylating agent.
- Metabolic modification by the allyl group leads to diverse tumor outcomes in different organs.