Formation of direct-acting mutagens from mixtures of N-nitrosomorpholine and carboxylates by UVA irradiation

Previously, we found that a directly mutagenic compound is produced from N-nitrosopiperidine (NPIP) in phosphate buffer on exposure to near-ultraviolet light (UVA) and we identified its structure as α-hydroxy-N-nitrosopiperidine phosphate ester. In the present study, we show that a similar photoactivation of an N-nitrosamine can take place with carboxylates in place of phosphate. When a neutral solution of a mixture of N-nitrosomorpholine (NMOR) and sodium acetate was irradiated with UVA, the solution became directly mutagenic towards Salmonella typhimurium TA1535. O⁶-Alkylguanine-DNA alkyltransferase-deficient strains of S. typhimurium showed remarkably higher mutagenesis responses to this mutagen than the proficient strains. Citrate, succinate, and several other biological carboxylates were also effective in producing the mutagens. Since a treatment of the 'NMOR plus acetate' photoproduct with carboxylic ester hydrolase resulted in a loss of the mutagenicity, the active principle is suggested to be an acetate-esterified derivative of NMOR. The role of the esters as intermediates in the photomutagenesis of nitrosamines is discussed.