Toggle Main Menu Toggle Search

Open Access padlockePrints

Evidence for phosphate adducts in DNA from mice treated with 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK)

Lookup NU author(s): Dr Alistair Henderson, Emeritus Professor Bernard Golding


Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


The weakly alkylating capacity of phosphotriesters (PTE) has been used for the determination of adducts to phosphate groups in DNA by specific transfer to the strongly nucleophilic compound cob(I)alamin [Cbl(I)]. When enzymatically degraded liver DNA from mice treated with 1-(N-methyl-N-nitrosamino)-4-(3-[H-3]pyridyl)-4-oxobutane ([H-3]NNK) was added to Cbl(I), a 4-(3-[H-3]pyridyl)-4-hydroxy-1-butyl-cobalamin ([H-3]PHB-Cbl) complex was formed and determined by HPLC and liquid scintillation counting. The PHB-Cbl formed was compared with a synthetic standard verified by LC/MS and H-1 NMR and corresponds to phosphate adducts formed from the pyridyloxobutylating species from NNK and from the pyridylhydroxybutylating species from NNAL, NNK being to a large extent converted to NNAL in vivo. It was concluded that about 22% of the total level of pyridyl (oxo or hydroxy) butyl adducts to DNA was bound to phosphate groups.

Publication metadata

Author(s): Haglund J, Henderson AP, Golding BT, Tornqvist M

Publication type: Article

Publication status: Published

Journal: Chemical Research in Toxicology

Year: 2002

Volume: 15

Issue: 6

Pages: 773-779

ISSN (print): 0893-228X

ISSN (electronic): 1520-5010

Publisher: American Chemical Society


DOI: 10.1021/tx015542o


Altmetrics provided by Altmetric