Whole-body hyperthermia and ADPRT inhibition in experimental treatment of brain tumors.
Malignant primary brain tumors have hitherto been incurable. One reason for this may be the migrating tumor cells that spread into the surrounding normal brain, creating the basis for inevitable recurrences. Therefore, local therapy may have a temporary effect, but for a cure, the treatment must reach all the tumor cells. Whole-body hyperthermia (WBH) is such a general treatment, which we have studied in a rat glioma model. Cells of the RG2 rat glioma cell line were inoculated in the right caudate nucleus of Fischer-344 rats, which were then either controls or treated with WBH, induced by a radiant heat device for 4-5 sessions of 30 min at body temperature 42 degrees C (rectal), and/or nicotinamide (NAM), an effective radiosensitizer in animal tumor models and an inhibitor of ADPRT (poly adenosine diphosphate ribosyl transferase), a chromatin-bound enzyme suggested to be important in the DNA repair system. We have shown that WBH 42 degrees C alone, or in combination with NAM, has no effect upon tumor growth if a larger number of RG2 cells (5,000) are inoculated. If only 1,000 cells are inoculated, a significant inhibitory effect (p < 0.05) is observed on tumor growth as compared to the untreated control animals. Thus, WBH is feasible, and in some circumstances effective, in a rat glioma model. WBH in combination with other therapies influencing cell metabolism may be of value in future postoperative treatment of human malignant brain tumors.
Salford
L G
LG
Department of Neurosurgery, Lund University Hospital, Sweden.
Brun
A
A
Kjellén
E
E
Pero
R W
RW
Persson
R B
RB
D000818:Animals; D001254:Astrocytoma / Q000188:drug therapy* / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D003131:Combined Modality Therapy; D004260:DNA Repair / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005910:Glioma; D006979:Hyperthermia, Induced; D008297:Male; D009368:Neoplasm Transplantation; D009536:Niacinamide / Q000494:pharmacology*; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D014407:Tumor Cells, Cultured / Q000637:transplantation
D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D009536:Niacinamide; D011064:Poly Adenosine Diphosphate Ribose; D011065:Poly(ADP-ribose) Polymerases