Formation of formaldehyde adducts in the reactions of DNA and deoxyribonucleosides with alpha-acetates of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and N-nitrosodimethylamine (NDMA)

Chemical Research in Toxicology
Guang ChengStephen S Hecht

Abstract

The cytochrome P450-mediated alpha-hydroxylation of the carcinogenic nitrosamines N-nitrosodimethylamine (NDMA, 1), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK, 6a), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL, 6b) produces diazonium ions and formaldehyde. The DNA-binding properties of the diazonium ions have been thoroughly characterized, and there is no doubt that they are critical in cancer induction by these nitrosamines. However, the possibility of additional DNA damage via released formaldehyde has not been reported. In this study, we used acetoxymethylmethylnitrosamine (5), 4-(acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone (10a), and 4-(acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanol (10b) as stable precursors to the alpha-hydroxymethylnitrosamines that would be formed in the metabolism of NDMA, NNK, and NNAL. These alpha-acetates were incubated with calf thymus DNA in the presence of esterase at pH 7.0 and 37 degrees C. The DNA was isolated and enzymatically hydrolyzed to deoxyribonucleosides, and the hydrolysates were analyzed by liquid chromatography-electrospray ionization-mass spectrometry-selected ion monitoring for formaldehyde DNA adducts. Convincing evidence for the formation of the for...Continue Reading

References

Nov 1, 1990·Chemical Research in Toxicology·L K KeeferP P Roller
Jan 1, 1973·Progress in Nucleic Acid Research and Molecular Biology·M Y Feldman
Jun 8, 1984·Journal of Chromatography·F A BelandR H Heflich
Jun 24, 1998·Chemical Research in Toxicology·S S Hecht
Apr 16, 2002·Chemical Research in Toxicology·Richard N Loeppky, Petra Goelzer
Sep 22, 1956·Nature·A H DUTTON, D F HEATH
Dec 1, 1958·The Biochemical Journal·P N MAGEE, M VANDEKAR
Oct 20, 2006·The Journal of Biological Chemistry·Jeong-Yun ChoiF Peter Guengerich

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Citations

Nov 30, 2006·Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco·Alison B BrelandThomas Eissenberg
Feb 18, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Dennie G A J HebelsTheo M C M de Kok
Feb 24, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Kun LuJames A Swenberg
Jul 1, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Lois Lehman-McKeeman
Dec 18, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·James A SwenbergThomas B Starr
Mar 24, 2016·Analytical and Bioanalytical Chemistry·Maria RajaSonia Sentellas
Jun 17, 2020·Archives of Toxicology·Andrea HartwigGerhard Eisenbrand
May 16, 2020·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·M AmararathnaH P Vasantha Rupasinghe
May 15, 2021·Journal of Pharmaceutical Sciences·Bodin Tuesuwan, Vorasit Vongsutilers
Sep 27, 2013·Chemical Research in Toxicology·Lisa A PetersonAnthony E Pegg

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