Department of Pharmacology
Alkylation; *DNA Damage; *DNA Repair; *Dinucleoside Phosphates; Escherichia coli; Ethylnitrosourea; *Lomustine; Poly A; *Poly T; *Polydeoxyribonucleotides; *Thymine Nucleotides
Life Sciences | Medicine and Health Sciences
The alkylation of phosphates in DNA by therapeutically active haloethylnitrosoureas was studied by reacting N-chloroethyl-N-nitrosourea (CNU) with dTpdT, separating the products by HPLC, and identifying them by co-chromatography with authentic markers. Both hydroxyethyl and chloroethyl phosphotriesters of dTpdT were identified; a similar reaction between CNU and dTR yielded 3-hydroxyethyl and 3-chloroethyl dTR as the major products of ring alkylation. A DNA-like substrate for repair studies was synthesized by reacting 14C-labelled N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosourea (14C-CCNU) with poly dT and annealing the product to poly dA. An extract of E. coli strain BS21 selectively transferred a chloroethyl group from one of the chloroethyl phosphotriester isomers in this substrate to the bacterial protein; chemical instability of the hydroxyethyl phosphotriesters precluded definite conclusions about the repair of this product.
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Citation: Nucleic Acids Res. 1988 Jun 24;16(12):5661-72.
Nucleic acids research
Carter, Christopher A.; Kirk, Marion C.; and Ludlum, David B., "Phosphotriester formation by the haloethylnitrosoureas and repair of these lesions by E. coli BS21 extracts" (1988). Open Access Articles. 1714.