DNA-strand breaks associated with halogenated pyrimidine incorporation

Mutat Res. 1984 Mar-Apr;131(3-4):129-36. doi: 10.1016/0167-8817(84)90052-x.

Abstract

The alkaline elution of bromodeoxyuridine-containing (BrdUrd) DNA and chlorodeoxyuridine-containing ( CldUrd ) DNA was studied in two CHO lines, the parental AA8 and a mutant line, EM9 , which has a defect in repairing strand breaks and a 12-fold elevated baseline frequency of SCE. BrdUrd-DNA was found to have alkali-labile sites as well as direct breaks, neither of which were increased significantly by prior treatment of AA8 cells with an inhibitor (benzamide) or poly(adenosine diphosphoribose) polymerase. CldUrd -DNA, which gives higher frequencies of SCEs than BrdUrd-DNA, had more strand breaks than BrdUrd-DNA in AA8 cells after treatment with benzamide, while without benzamide there was no difference. The accumulation of breaks in CldUrd -DNA by benzamide was shown to occur rapidly, to reach a maximum by 90 min, and to be readily reversible after benzamide removal. Under all conditions, EM9 cells had more strand breaks than AA8 . These observed differences in strand breaks were not due to differences in incorporation efficiencies. For the different halogenated pyrimidines and cell types, there was a good correlation between the number of strand breaks and reduction in plating efficiencies.

Publication types

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

MeSH terms

  • Animals
  • Benzamides / toxicity
  • Bromodeoxyuridine / metabolism
  • Bromodeoxyuridine / toxicity*
  • Cell Line
  • Cricetinae
  • Cricetulus
  • DNA Repair
  • DNA Replication / drug effects*
  • Deoxyuridine / analogs & derivatives*
  • Deoxyuridine / metabolism
  • Deoxyuridine / toxicity
  • Female
  • Kinetics
  • Mutation
  • Ovary
  • Sister Chromatid Exchange / drug effects

Substances

  • Benzamides
  • 2'-chloro-2'-deoxyuridine
  • benzamide
  • Bromodeoxyuridine
  • Deoxyuridine