N-nitrosamines, which are classified as carcinogens by IARC and US EPA, can be easily found in various foods. They are reaction products between nitrogen oxide and secondary amines, but can also be generated during fermentation. Ever since the 1960s, when nitrite, used as a preservative in processed meats, was suspected to generate N-nitrosamines, the usage of the food additive has been debated...

The pharmacokinetics of N-nitrosodimethylamine was studied in patas monkeys following i.v. doses of 0.5, 1.0, and 5.0 mg/kg and a p.o. dose of 1.0 mg/kg, and in Swiss mice at i.v. doses of 1.0 and 2.0 mg/kg. In the patas monkey the pharmacokinetics was linear over the i.v. dose range studied. The mean clearance (Cl), steady-state volume of distribution (Vss), mean residence time, and eliminatio...

Patients and prescribers have recently been affected by interruptions to the supply of all formulations H2 antagonist ranitidine as a result possible contamination with N-nitrosodimethylamine. Here, Marco Motta Mike Wilcock present outcomes their study evaluating implications these shortages for patients taking from six GP practices in Cornwall.

The metabolic dealkylation of nine nitrosodialkylamines, including five symmetrical (nitrosodimethylamine, nitrosodiethylamine, nitrosodipropylamine, nitrosodibutylamine and nitrosodiamylamine) and four asymmetrical nitrosodialkylamines (nitrosomethylethylamine, nitrosomethylpropylamine, nitrosomethylbutylamine and nitrosomethylamylamine), was investigated in 14 samples of human liver microsome...

Previous studies have shown that a diet high in fat and marginally deficient in lipotropes enhances aflatoxin B] hepatocarcinogenesis and depresses hepatic drug metabolism in rats. In this study we have compared induction of tumors by jV-nitrosodimethylamine, ./V-nitrosodiethylamine, or jV-nitrosodibutylamine in normal or marginally lipotrope-deficient rats fed a high-fat diet. The deficiency s...

The metabolism of nitrosamines by microsomal cytochrome P-450 (P-450) isozymes was studied in a reconstituted monooxygenase system. P-450 LM2, LM3a, LM3b and LM3c, LM4, and LM6 were purified, respectively, from the livers of phenobarbital-treated, ethanol-treated, untreated, isosafrole-treated, and imidazole-treated rabbits. Of these isozymes, LM3a had the highest N-nitrosodimethylamine demethy...

A pharmacokinetic model was constructed to describe the absorption, distribution, and metabolic clearance of N-nitrosodimethylamine. The model is composed of two compartments, total body water and the liver, which are linked by blood flow. Metabolic clearance is presumed to occur only in the liver. Liver clearance kinetics was determined with isolated perfused livers. Clearance appeared to obey...

Perinatal nitrosamine exposures may contribute to childhood cancer risk. To test primate fetal susceptibility to formation of cancer initiation-related DNA adducts from nitrosamines, pregnant patas monkeys were given 1.0 or 0.1 mg/kg N-nitrosodimethylamine. Appreciable levels of the promutagenic O6-methylguanine adduct occurred in placental and fetal liver DNA after both doses and were lower bu...