Liquid chromatography--electrospray ionization mass spectrometric detection of an ethenodeoxyguanosine adduct and its hemiaminal precursors in DNA reacted with alpha-acetoxy-N-nitrosopiperidine and cis-4-Oxo-2-pentenal.
N-Nitrosopiperidine, a carcinogenic cyclic nitrosamine that occurs in the diet and may be formed endogenously, is believed to be metabolically activated by alpha-hydroxylation. The DNA reactive compounds that could be formed in this process have been studied using alpha-acetoxy-N-nitrosopiperidine as a model. Previous studies have shown that 4-oxo-2-pentenal is one product of the hydrolysis of alpha-acetoxyNPIP and that it reacts with deoxyguanosine to produce 7-(2-oxopropyl)-5,9-dihydro-9-oxo-3-beta-D-deoxyribofuranosylimidazo+ ++ [1,2-a]purine (7-(2-oxopropyl)-1,N2-ethenodG). Several other products were formed in that reaction, and these have now been identified as diastereomers of 7-(2-oxopropyl)-5-hydroxy-5,6,7,9-tetrahydro-9-oxo-3-beta-D- deoxyribofuranosylimidazo[1,2-a]purine, the hemiaminal precursors to 7-(2-oxopropyl-1,N2-ethenodG. Their structures were characterized by electrospray ionization mass spectrometry (ESI-MS), and by reduction with NaBH4 followed by hydrolysis to 7-(2-hydroxypropyl)-5,6,7,9-tetrahydro-9-oxoimidazol [1,2-a]purine, which was characterized by 1H-NMR, MS, and UV. The presence of 7-(2-oxopropyl)-1,N2-ethenodG and its hemiaminal precursors in DNA reacted with either alpha-acetoxy-N-nitrosopiperidine or cis-4-oxo-2-pentenal was confirmed by LC-ESI-MS/MS. The results of this study demonstrate that ethenodG adducts and their precursors are present in DNA reacted with alpha-acetoxy-N-nitrosopiperidine, which suggests a possible basis for the unique carcinogenic properties of nitrosamine.
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American Health Foundation, Valhalla, New York 10595, USA.
Young-Sciame
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Hecht
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D000171:Acrolein / Q000031:analogs & derivatives* / Q000737:chemistry; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002273:Carcinogens / Q000737:chemistry*; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D018736:DNA Adducts / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis / Q000737:chemistry*; D003850:Deoxyribonuclease I / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D006863:Hydrogen-Ion Concentration; D006900:Hydroxylation; D009682:Magnetic Resonance Spectroscopy; D009153:Mutagens / Q000737:chemistry*; D009603:Nitroso Compounds / Q000737:chemistry*; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D010880:Piperidines / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D013950:Thymus Gland / Q000737:chemistry; D014316:Tritium
D002273:Carcinogens; D018736:DNA Adducts; D009153:Mutagens; D009603:Nitroso Compounds; D010880:Piperidines; D014316:Tritium; C054579:1,N(2)-ethenodeoxyguanosine; C078330:alpha-acetoxy-N-nitrosopiperidine; C046802:acetylacrolein; D000171:Acrolein; D003850:Deoxyribonuclease I; D000469:Alkaline Phosphatase; D010727:Phosphoric Diester Hydrolases; D043264:Phosphodiesterase I; D003849:Deoxyguanosine