title: Phosphotriester formation by the haloethylnitrosoureas and repair of these lesions by E. coli BS21 extracts.
abstract: 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.
authors.affiliation: Department of Pharmacology, UMass Medical School, Worcester 01655.
authors.forename: C A
authors.initials: CA
authors.lastname: Carter
authors.forename: M C
authors.initials: MC
authors.lastname: Kirk
authors.forename: D B
authors.initials: DB
authors.lastname: Ludlum
mesh_terms: D000478:Alkylation; D004249:DNA Damage; D004260:DNA Repair; D015226:Dinucleoside Phosphates; D004926:Escherichia coli / Q000235:genetics*; D005038:Ethylnitrosourea / Q000031:analogs & derivatives*; D008130:Lomustine; D011061:Poly A; D011071:Poly T; D011089:Polydeoxyribonucleotides; D013942:Thymine Nucleotides
chemical_list: D015226:Dinucleoside Phosphates; D011089:Polydeoxyribonucleotides; D013942:Thymine Nucleotides; C017758:thymidylyl-(3'-5')-thymidine; C017139:1-(2-chloroethyl)-1-nitrosourea; D011061:Poly A; D011071:Poly T; C015465:poly(dA); D008130:Lomustine; D005038:Ethylnitrosourea