title: Effect of hyperthermia in vitro and in vivo on adenine and pyridine nucleotide pools in human peripheral lymphocytes.
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.affiliation: Department of Human Oncology, University of Wisconsin, Clinical Science Center, Madison 53792.
authors.forename: H I
authors.initials: HI
authors.lastname: Robins
authors.forename: G G
authors.initials: GG
authors.lastname: Jonsson
authors.forename: E L
authors.initials: EL
authors.lastname: Jacobson
authors.forename: C L
authors.initials: CL
authors.lastname: Schmitt
authors.forename: J D
authors.initials: JD
authors.lastname: Cohen
authors.forename: M K
authors.initials: MK
authors.lastname: Jacobson
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D006979:Hyperthermia, Induced; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000378:metabolism*; D008954:Models, Biological; D009243:NAD / Q000378:metabolism*; D009369:Neoplasms / Q000097:blood / Q000628:therapy
chemical_list: D009243:NAD; D000255:Adenosine Triphosphate