The effect of nitroimidazole and nitroxyl radiosensitizers on the post-irradiation synthesis of DNA

Int J Radiat Biol Relat Stud Phys Chem Med. 1976 Sep;30(3):247-61. doi: 10.1080/09553007614551021.

Abstract

The modification of DNA damage by three radiosensitizing drugs, present during gamma-irradiation of hypoxic Chinese hamster cells, was investigated. Both 2-methyl-5-nitroimidazole-1-ethanol (metronidazole) and 1-(2-nitro-1-imidazole)-3-methoxy-2-propranol (Ro-07-0582) were found to cause large increases in the yield of DNA single-strand breaks (SSB); triacetoneamine-N-oxyl (TAN) was found to have only a small effect on SSB production. The three drugs tested did not inhibit the rejoining of SSB. A pulse label and chase procedure was used to examine post-irradiation DNA synthesis. TAN present during irradiation under hypoxia was found to cause interruptions in subsequent DNA synthesis. Metronidazole and Ro-07-0582 had no effect on post-irradiation DNA synthesis. In addition, the effects of pre- and post-irradiation exposure to TAN were investigated, since these treatments have shown increased cell-killing in survival studies. TAN pre- and post-treatments were found to have no significant effect on subsequent DNA synthesis.

MeSH terms

  • Cells, Cultured / drug effects
  • Cells, Cultured / radiation effects
  • Cobalt Radioisotopes
  • Cyclic N-Oxides / pharmacology*
  • DNA Repair / drug effects*
  • DNA, Single-Stranded / radiation effects
  • Dose-Response Relationship, Radiation
  • Gamma Rays
  • Nitroimidazoles / pharmacology*
  • Radiation-Sensitizing Agents / pharmacology*
  • Triacetoneamine-N-Oxyl / pharmacology*

Substances

  • Cobalt Radioisotopes
  • Cyclic N-Oxides
  • DNA, Single-Stranded
  • Nitroimidazoles
  • Radiation-Sensitizing Agents
  • Triacetoneamine-N-Oxyl