Metabolism of Acyclic and Cyclic N-Nitrosamines by Cultured Human Colon

Abstract

Cultured human colon mucosa was found to metabolize both acyclic and cyclic N-nitrosamines as measured by 14C-CO2 formation and reaction of the activated moieties with cellular macromolecules. Dimethylnitrosamine and N-nitrosopyrrolidine were metabolized by explants from all patients studied. A positive correlation between binding of dimethylnitrosamine to DNA and CO2-formation was observed. DMN alkylated DNA in both O-6 and N-7 position of guanine. However, most of the radioactivity was associated with an acid labile compound. High binding levels of N,N'-dinitrosopiperazine to protein without concomitant binding to DNA were detected. Inter-individual variation in both binding level to DNA and ability to metabolize the different N-nitrosamines was observed.<br/><br/>We would like to thank Drs. U. Saffiotti, G. Stoner, and T. Bowden for valuable comments, Ms. R. Schwartz for technical assistance, and Mrs. M. Bellman for secretarial assistance.