Abstract |
Hyperthermia has been shown in vitro and in vivo to potentiate the effects of ionizing irradiation. Previous studies found that hyperthermia alters the metabolism of adenosine diphosphate ( ADP)-ribose polymers required for recovery from DNA damage and that poly(ADP-ribose) polymerase activity is very sensitive to cellular nicotinamide-adenine dinucleotide ( NAD) levels. Thus, the effect of 41.8 degrees C hyperthermia in vitro and in vivo on NAD and adenosine triphosphate ( ATP) levels was studied in human peripheral lymphocytes. In vitro studies showed significant decreases in oxidized NAD ( NAD+) and ATP levels after heating that simulated a clinical whole-body hyperthermia (WBH) treatment. This nucleotide depletion could not be attributed to nucleotide leakage or increased enzymatic NAD+ consumption. As the reduction of NAD observed was sufficient to decrease poly(ADP-ribose)polymerase activity by 50%, the studies were extended to clinica cases. Cellular NAD+ and ATP were measured in previously stored lymphocytes obtained from four patients before and after WBH; a statistically significant decrease in NAD+ was observed after WBH which quantitatively agreed with the in vitro results. Based on these results a prospective study was done in three patients; NAD+ was extracted immediately on sample collection, and the kinetics of WBH-induced NAD depletion were studied. These data, which agree quantitatively with the laboratory results, are presented.
|
Authors | H I Robins, G G Jonsson, E L Jacobson, C L Schmitt, J D Cohen, M K Jacobson |
Journal | Cancer
(Cancer)
Vol. 67
Issue 8
Pg. 2096-102
(Apr 15 1991)
ISSN: 0008-543X [Print] United States |
PMID | 2004328
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
|
Chemical References |
- NAD
- Adenosine Triphosphate
|
Topics |
- Adenosine Triphosphate
(metabolism)
- Cells, Cultured
- Humans
- Hyperthermia, Induced
- In Vitro Techniques
- Lymphocytes
(metabolism)
- Models, Biological
- NAD
(metabolism)
- Neoplasms
(blood, therapy)
|