Radiation-induced effect of adenine (vitamin B4) on mitomycin C activity. In vitro experiments.
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.
Hartmann
Johannes
J
Medical University of Vienna, Waehringer Gürtel 18-20, A-1090 Wien, Austria.
Getoff
Nikola
N
D000225:Adenine / Q000494:pharmacology* / Q000528:radiation effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004357:Drug Synergism; D005561:Formates / Q000737:chemistry / Q000378:metabolism; D005609:Free Radicals / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D016685:Mitomycin / Q000494:pharmacology*; D009609:Nitrous Oxide / Q000737:chemistry / Q000378:metabolism; D011837:Radiation-Protective Agents / Q000494:pharmacology
D005561:Formates; D005609:Free Radicals; D011837:Radiation-Protective Agents; C030544:formic acid; D016685:Mitomycin; D000225:Adenine; D009609:Nitrous Oxide