Chemical synthesis and detection of the cross-link 1-[N3-(2'-deoxycytidyl)]-2-[N1-(2'-deoxyguanosinyl)]ethane in DNA reacted with 1-(2-chloroethyl)-1-nitrosourea

Chem Res Toxicol. 1993 Jul-Aug;6(4):434-8. doi: 10.1021/tx00034a008.

Abstract

We have synthesized 1-[N3-(2'-deoxycytidyl)]-2-[N1-(2'-deoxyguanosinyl)]ethane and confirmed its structure by ultraviolet and high-resolution mass spectrometry. Treatment of calf thymus DNA with [3H](2-chloroethyl)-1-nitrosourea resulted in the formation of at least 13 DNA alkylation products that were separated by HPLC. 1-[N3-(2'-Deoxycytidyl)]-2-[N1-(2'-deoxyguanosinyl)]ethane was a minor product, accounting for 3.4% of the total DNA alkylation. The DNA cross-link 1,2-di-N7-guanylethane was formed to a similar extent (3.2%). Other minor alkylation products were O6-(2-hydroxyethyl)deoxyguanosine (1.5%) and N1-(2-hydroxyethyl)deoxyguanosine (3.8%). The principal alkylation products formed by 1-(2-chloroethyl)-1-nitrosourea (CNU) treatment of DNA were N7-(2-hydroxyethyl)guanine (36.4%), N7-(2-chloroethyl)guanine (14.6%), and phosphotriesters (26.1%). The development of analytical procedures to measure DNA alkylation products after treatment with CNU will allow us to investigate factors influencing their formation and repair.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkylation
  • Animals
  • Cattle
  • Chromatography, High Pressure Liquid
  • Cross-Linking Reagents
  • DNA / analysis*
  • DNA / drug effects
  • Deoxyribonucleosides / analysis
  • Deoxyribonucleosides / chemical synthesis*
  • Deoxyribonucleosides / isolation & purification
  • Ethylnitrosourea / analogs & derivatives*
  • Ethylnitrosourea / pharmacology
  • Mass Spectrometry
  • Spectrophotometry, Ultraviolet

Substances

  • Cross-Linking Reagents
  • Deoxyribonucleosides
  • 1-(2-chloroethyl)-1-nitrosourea
  • 1-(N(3)-deoxycytidyl)-2-(N(1)-deoxyguanosinyl)ethane
  • DNA
  • Ethylnitrosourea