Related Experiment Videos
Metabolism and mutagenicity of N-nitroso-2-methoxy-2,6-dimethylmorpholine in hamsters
Abstract:
N-Nitroso-2-methoxy-2,6-dimethylmorpholine (MeNDMM) was derived from the cyclic form of N-nitroso-(2-hydroxypropyl)(2-oxopropyl)amine (HPOP), a proposed proximate pancreatic carcinogen for the hamster. MeNDMM was metabolized in vivo by noninbred Syrian golden hamsters to HPOP, which was excreted in urine. In vitro metabolism produced HPOP by cytochrome P450-mediated oxidative demethylation. MeNDMM and HPOP were similarly mutagenic in the Ames Salmonella typhimurium assay, in which hamster liver preparations were used for metabolic activation. MeNDMM, due to its metabolism to HPOP, is probably also a pancreatic carcinogen in the hamster.
Insights
N-Nitroso-2-methoxy-2,6-dimethylmorpholine (MeNDMM) metabolizes to N-nitroso-(2-hydroxypropyl)(2-oxopropyl)amine (HPOP) in hamsters. This pathway suggests MeNDMM is also a pancreatic carcinogen, similar to HPOP.
Area of Science:
- Toxicology
- Carcinogenesis
- Metabolism
Background:
- N-nitroso-(2-hydroxypropyl)(2-oxopropyl)amine (HPOP) is a suspected pancreatic carcinogen in hamsters.
- N-Nitroso-2-methoxy-2,6-dimethylmorpholine (MeNDMM) is a derivative of HPOP's cyclic form.
Purpose of the Study:
- To investigate the metabolism and mutagenicity of MeNDMM.
- To determine if MeNDMM acts as a pancreatic carcinogen in hamsters.
Main Methods:
- In vivo and in vitro metabolism studies in Syrian golden hamsters.
- Cytochrome P450-mediated oxidative demethylation assays.
- Ames Salmonella typhimurium mutagenicity assay with hamster liver preparations.
Main Results:
- MeNDMM was metabolized to HPOP in vivo and excreted in urine.
- In vitro studies confirmed HPOP production via cytochrome P450.
- Both MeNDMM and HPOP demonstrated similar mutagenicity in the Ames assay.
Conclusions:
- MeNDMM is metabolized to HPOP, a known proximate pancreatic carcinogen.
- MeNDMM is likely also a pancreatic carcinogen in hamsters due to its metabolic conversion to HPOP.