Radiation-induced effect of adenine (vitamin B4) on mitomycin C activity. In vitro experiments

Anticancer Res. 2006 Jul-Aug;26(4B):3005-10.

Abstract

The radiation-induced biological behavior of adenine (vitamin B4) was investigated in vitro under various conditions, implementing breast cancer cells (MCF-7 line) as a model. In aerated media (46% OH and 54% O2*-) at pH=7.4, adenine at low concentration (2 micromol) acted as an efficient radiation-protecting agent. At higher concentration, however, it inhibited cytostatic properties with regard to cancer cells. This double-track activity is based on its chemical structure. Similar features of adenine were also observed in air-free (46% OH, 44% e- aq, 10% H) as well as in media saturated with N2O (90% OH, 10% H), but with different efficiencies. In the presence of mitomycin C (MMC), adenine retained its double-track behavior. Hence, adenine and MMC compete for the e- aq, but the electronically excited adenine molecules can transfer electrons to MMC, leading to the additional formation of active MMC-. By implementation of formate for the conversion of OH and H into the transient *COO-, which subsequently transfers electron to MMC, a highest efficiency of MMC- was obtained.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / pharmacology*
  • Adenine / radiation effects*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / radiotherapy*
  • Cell Line, Tumor
  • Combined Modality Therapy
  • Drug Synergism
  • Formates / chemistry
  • Formates / metabolism
  • Free Radicals / chemistry
  • Free Radicals / metabolism
  • Humans
  • Mitomycin / pharmacology*
  • Nitrous Oxide / chemistry
  • Nitrous Oxide / metabolism
  • Radiation-Protective Agents / pharmacology

Substances

  • Formates
  • Free Radicals
  • Radiation-Protective Agents
  • formic acid
  • Mitomycin
  • Adenine
  • Nitrous Oxide