Effect of mild hyperglycemia +/- meta-iodo-benzylguanidine on the radiation response of R3230 Ac tumors.
The effects of glucose or meta-iodo-benzylguanidine (MIBG) on oxygen utilization (QO2) of several tumor cell lines were studied using a Clark-type electrode chamber. For in vivo studies, rats bearing R3230 Ac rat mammary adenocarcinomas were utilized. To evaluate changes in tumor oxygenation induced by glucose or MIBG, intratumoral pO2 and skeletal muscle pO2 were measured using Eppendorf Histography. To find the effect of mild hyperglycemia (i.p., 1 g/kg) +/- MIBG (i.p., 20 mg/kg) on the radiation response, a growth delay assay was used. Glucose alone produced a approximately 20% inhibition of QO2 in several tumor cells we tested except Q7 tumor cells. MIBG inhibited QO2 in R3230 Ac tumors. The median tumor pO2 for glucose + MIBG was increased from 5.3 mm Hg to 13.8 mm Hg. We hypothesized that combined treatment with glucose + MIBG significantly enhanced radiation-induced tumoricidal effects on R3230 Ac tumors, mainly due to reduction in QO2 and increase in tumor pO2.
Lee
Intae
I
Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Glickson
Jerry D
JD
Dewhirst
Mark W
MW
Leeper
Dennis B
DB
Burd
Randy
R
Poptani
Harish
H
Nadal
Lydie
L
McKenna
W Gillies
WG
Biaglow
John E
JE
D019797:3-Iodobenzylguanidine / Q000494:pharmacology*; D000230:Adenocarcinoma / Q000378:metabolism*; D000818:Animals; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology*; D007668:Kidney / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D014407:Tumor Cells, Cultured
D019797:3-Iodobenzylguanidine; D005947:Glucose; D010100:Oxygen