Davis, James

Hobson, Stephen

McCoy, Madeline

Rippey, Chloe

Liberty University Digital Commons

AbstractStomach cancer is estimated to affect 27,600 patients this year and to claim the lives of 11,010 of those patients. The human cost of this disease highlights the need for an intervention which will be capable of averting a diagnosis of stomach cancer. The gut forms the compound N-methyl-N-nitrosourea (NMU) from ingested foods containing nitrates preservatives such as deli meats. The NMU compound decomposes into a methyl diazonium salt in the low pH of the stomach. This methyl diazonium salt specifically targets guanine at the O-6 position for methylation. The methylation of guanine in DNA leads to mispairing mutations which have been linked to stomach cancer. NMU was successfully synthesized by reacting N-methylurea with other substrates. Reaction conditions were developed in order to demonstrate the methylating capability of the synthesized NMU and the inhibiting of this methylation via the introduction of dietary supplements and flavonoids. The success of NMU to methylate guanine as it occurs in the gut was effectively demonstrated using HPLC analysis. An HPLC protocol for guanine and O-6 methyl guanine standards were developed and optimized. Using the same reaction conditions developed for the control, ascorbic acid (vitamin C) was shown to effectively inhibit the methylation of guanine, while vitamin E demonstrated little effect on methylation. The HPLC analysis for the ascorbic acid and the vitamin E were conducted under the same conditions as the control and were compared to the control. A standard guanine curve from HPLC will be developed, and the inhibiting effects of other flavonoids will be tested and reported. The results of these tests will inform the design and synthesis of new compounds for research. 

Inhibiting Nitroso Related Methylation of Guanine Using Dietary Supplements and Flavonoids

Abstract

Similar works

Full text

Available Versions

Liberty University Digital Commons