Nicotinamide, Fluosol DA and Carbogen: a strategy to reoxygenate acutely and chronically hypoxic cells in vivo.
The effect of Nicotinamide and/or treatment with Fluosol DA and Carbogen breathing on the radiation response of 500-750 mg SCCVII and KHT tumours has been evaluated. Pretreatment with Fluosol DA/Carbogen or Nicotinamide resulted in relatively modest enhancements of radiation damage with enhancement factors of 1.1 and 1.3 being observed using an in vivo/in vitro clonogenic end-point. A combination of Nicotinamide and Fluosol DA/Carbogen resulted in a larger enhancement factor of 1.6 over the radiation dose ranges studied. These modification factors reflect a value close to that expected for a fully aerobic response in this survival range. Growth delay studies in the SCCVII tumour provided similar results. Using a recently developed fluorescence activated cell sorting technique, which utilizes the in vivo pharmacokinetic and DNA binding properties of the bisbenzamide stain Hoechst 33342, the effect of Nicotinamide and/or Fluosol DA/Carbogen schedules on the occurrence of acute hypoxia was assessed. The results clearly show that Nicotinamide significantly reduces the amount of 'acute hypoxia', but has a lesser effect on 'chronic' hypoxic cells. However, combinations of Nicotinamide and Fluosol DA/Carbogen significantly increase the response of both 'acutely' and 'chronically hypoxic' cells. The results provide evidence that a combination of Nicotinamide and Fluosol DA/Carbogen can provide an effective way of reoxygenating both acutely and chronically hypoxic cells.
Chaplin
D J
DJ
Medical Biophysics Unit, B.C. Cancer Research Centre, Vancouver, Canada.
Horsman
M R
MR
Aoki
D S
DS
D000818:Animals; D002245:Carbon Dioxide / Q000494:pharmacology*; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D015687:Cell Hypoxia / Q000187:drug effects* / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D005466:Fluorocarbons / Q000494:pharmacology*; D006895:Hydroxyethyl Starch Derivatives; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D009536:Niacinamide / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D012513:Sarcoma, Experimental / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy
D004338:Drug Combinations; D005466:Fluorocarbons; D006895:Hydroxyethyl Starch Derivatives; D011838:Radiation-Sensitizing Agents; D002245:Carbon Dioxide; D009536:Niacinamide; C017323:glucose, glycerol, hydroxyethyl starch, perfluorodecalin, perfluorotripropylamine, pluronic F-68, salts, yolk phospholipids drug combination; C011700:carbogen; D010100:Oxygen