Possible mechanisms involved in tumor radiosensitization following nicotinamide administration.
Despite continued interest in the administration of nicotinamide (NA) as a tumor-specific radiosensitizer (an effect thought to be related to increases in tumor blood flow and oxygenation), little is known about the underlying mechanism(s) of this effect. The aim of this study was to investigate metabolic changes following NA application in both tumor and normal tissues. Increased concentrations of NAD+ were measured in DS-sarcomas, liver, and kidney tissue, with no changes in concentrations in resting skeletal muscle. Further investigations also examined the concentrations of glucose, lactate, ATP, ADP and AMP in tumor and resting skeletal muscle tissue following NA application. Here, the only change detected was an increase in lactate levels in tumor tissue. The changes in NAD+ concentrations described correlate well with reported changes in tissue blood flow measured following NA. On the basis of changes in tumor blood flow, oxygenation and metabolite concentrations found in this and other recent studies, possible mechanisms for tumor radiosensitization following nicotinamide administration are considered.
Kelleher
D K
DK
Institute of Physiology and Pathophysiology, University of Mainz, Germany.
Vaupel
P W
PW
D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D009536:Niacinamide / Q000494:pharmacology*; D010100:Oxygen / Q000097:blood; D010108:Oxyhemoglobins / Q000032:analysis; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D012513:Sarcoma, Experimental / Q000098:blood supply / Q000378:metabolism / Q000532:radiotherapy*
D007773:Lactates; D010108:Oxyhemoglobins; D011838:Radiation-Sensitizing Agents; D009243:NAD; D009536:Niacinamide; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D005947:Glucose; D010100:Oxygen