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.
Nucleic Acids Res. 1988 Jun 24;16(12):5661-72.
Nucleic acids research
Carter CA, Kirk MC, Ludlum DB. (1988). Phosphotriester formation by the haloethylnitrosoureas and repair of these lesions by E. coli BS21 extracts. Open Access Publications by UMMS Authors. Retrieved from https://escholarship.umassmed.edu/oapubs/1714