PMID: 6160100Jan 1, 1980Paper

Metabolism of N-nitrosodimethylamine

IARC Scientific Publications
A E Pegg

Abstract

NDMA and NDEA are metabolized by a microsomal enzyme system that requires NADPH and oxygen. This metabolism leads to an unstable product which decomposes to yield a reactive alkylating species. This species is too reactive chemically to influence significantly organs other than those in which it was generated. Alkylation of cellular components, particularly DNA, is a critical event in the initiation of tumours by these carcinogens. The greatest capacity to metabolize these nitrosamines to alkylating agents is found in the liver, but other organs, including the oesophagus, lung and kidney, are also capable of activation. These organs may be more susceptible to alkylation than the liver because they have a lesser ability to catalyse the removal of 06-alkylguanine from their DNA. However, orally administered doses of NDMA and the NDMA formed by nitrosation reactions within the gastrointestinal tract are rapidly absorbed from the upper part of the small intestine and carried to the liver in the portal blood supply. When small doses are given in this way, the capacity of the liver to metabolize the carcinogen is sufficient that the nitrosamine is effectively cleared in a 'first-pass' effect, leaving very little to interact with othe...Continue Reading

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