Date of Award:

5-1989

Document Type:

Thesis

Degree Name:

Master of Science (MS)

Department:

Chemistry and Biochemistry

Committee

Lawrence H. Piette

Abstract

N-Nitrosamines and N-nitrosamides have been reported to be mutagenic. N-Nitrosamides are direct mutagens that need no activation to be mutagenic, whereas N-nitrosamines need to be enzymatically activated to exert their mutagenicity. Oxidative demethylation of nitrosamines is a commonly accepted activation mechanism. Another pathway of nitroso compounds, denitrosation, has recently been proposed. The mechanism of denitrosation, however, is still unknown.

The purpose of this study was to use a photo -reaction model to explore the possible denitrosation mechanism of N-nitroso compounds. An N-nitrosamine, N-nitrosomorpholi ne (NMOR), and an N-nitrosamide, N-methyl-N'-nitrosoguanidine (MMNG), were irradiated with long-wavelength UV light in the presence of phosphate. Denitrosation of these nitroso compounds occurred, and free radicals were generated during the photolysis of N-nitroso compounds. The free radical from NMOR is carbon centered, and the free radical from MNNG is nitrogen centered. They have different responses to phosphate. A stable mutagen is formed during the photolysis of NMOR in the presence of phosphate. The formation of this stable mutagen is through a free-radical mechanism. MNNG appears to be inactivated in terms of mutagenicity by the photodenitrosation. Free radicals produced during the photolysis of NMOR and MNNG are mutagenic through a direct radical interaction mechanism.

The results of this study indicate that the newly found pathway of N-nitroso compounds, denitrosation, may be related to a free-radical mechanism.

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