Assessing the formation and biological significance of selected environmental nitrosamines using model systems

Nitrosamines comprise a large class of potentially mutagenic, teratogenic and carcinogenic chemicals found in the environment as by-products of various manufacturing, agricultural and natural processes. Nitrosamines may form in the presence of an acid, nitrite and a suitable secondary or tertiary amine; these conditions can occur in the mammalian gastrointestinal tract. The focus of our research is the formation, stability and bioavailability of environmentally relevant nitrosamines, produced from the reaction of nitrite with dimethylamine, morpholine and atrazine, using different model systems. An in vitro model of the gastrointestinal tract is used to determine nitrosamine formation and inhibition of the reaction by vitamins. Determining how vitamins influence the formation of nitrosamines may contribute to cancer prevention and therapy measures. A chicken egg model is used to determine nitrosamine partitioning between a hydrophilic phase (albumin) and a lipophilic phase (yolk) via a biomembrane (Vitelline membrane). An understanding of the partitioning behavior of nitrosamines can be used to assess potential bioavailability, fate and impact. Preliminary results with the chicken egg model show that the selected nitrosamines partition from the albumin into the yolk where they are stable. An observed decrease in total nitrosamine with time may indicate denitrosation, releasing nitrous acid, which can decompose to nitrite and nitric oxide, an important biological messenger in development. Thus we also assess the impact of the nitrosamines on nitric oxide synthase activity and concentrations of nitric oxide to determine potential teratogenic effects. The information obtained from these studies should be invaluable for exposure and risk assessment.