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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, Professor Bernard Golding

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Abstract

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

URL: http://dx.doi.org/10.1021/tx015542o

DOI: 10.1021/tx015542o


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