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Lookup NU author(s): Dr Alistair Henderson,
Professor Bernard Golding
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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.
Author(s): Haglund J, Henderson AP, Golding BT, Tornqvist M
Publication type: Article
Publication status: Published
Journal: Chemical Research in Toxicology
ISSN (print): 0893-228X
ISSN (electronic): 1520-5010
Publisher: American Chemical Society
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