[The role of N-nitrosourea-induced changes in the nucleoid structure and activity of repair enzymes in the development of drug resistance in mice with leukemia L1210]

Biokhimiia. 1987 Aug;52(8):1335-43.
[Article in Russian]

Abstract

Using centrifugation of the nucleoid in a neutral sucrose gradient, the damages in the secondary structure of DNA and the activity of repair enzymes, such as DNA-polymerases alpha and beta and poly(ADP-riboso) polymerase, induced by 1-methyl-nitrosourea (MNU) and 1.3-bis (2-chloroethyl)-1-nitrosourea (BCNU) injected at maximal nonlethal single doses to mice bearing parent leukemia cells (L1210/0) and resistant to MNU and BCNU leukemia L1210 cells (L1210/MNU and L1210/BCNU), were studied. The MNU-induced production of single-strand breaks in L1210/0 and L1210/MNU cells was more conspicuous in newly replicated DNA than in those in preexisting DNA. A more fast repair of the damages in newly replicated DNA was detected in L1210/BCNU and especially in L1210/MNU leukemia cells as compared with L1210/0 cells. The data obtained suggest that there are prone errors in the repair of DNA template, since most of the single-strand breaks were revealed in the newly replicated DNA synthesized on the repaired DNA. The repair of DNA damages in L1210/BCNU and especially in L1210/MNU cells was accompanied by the activation of DNA-polymerases alpha and beta and poly(ADP-riboso)polymerase. Both DNA-polymerases--alpha and beta--were shown to be involved in repair of DNA damages induced by MNU and only DNA-polymerase beta was involved in the repair of damages induced by BCNU.

Publication types

  • English Abstract

MeSH terms

  • Animals
  • Carmustine / pharmacology*
  • Cell Nucleus / enzymology
  • DNA Repair / drug effects*
  • DNA, Neoplasm / biosynthesis
  • DNA, Neoplasm / drug effects*
  • DNA-Directed DNA Polymerase / metabolism
  • Drug Resistance
  • Enzyme Activation / drug effects
  • Leukemia L1210 / genetics
  • Leukemia L1210 / metabolism*
  • Methylnitrosourea / pharmacology*
  • Mice
  • Tumor Cells, Cultured

Substances

  • DNA, Neoplasm
  • Methylnitrosourea
  • DNA-Directed DNA Polymerase
  • Carmustine