Effects of combined photodynamic therapy and ionizing radiation on human glioma spheroids.
The effects of combined photodynamic therapy (PDT) and ionizing radiation are studied in a human glioma spheroid model. The degree of interaction between the two modalities depends in a complex manner on factors such as PDT irradiation fluence, fluence rate and dose of ionizing radiation. It is shown that gamma radiation and PDT interact in a synergistic manner only if both light fluence and gamma radiation dose exceed approximately 25 J cm(-2) and 8 Gy, respectively. Synergistic interactions are observed only for the lower fluence rate (25 mW cm(-2)) investigated. The degree of interaction appears to be independent of both sequence and the PDT or ionizing radiation time intervals investigated (1 and 24 h). Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assays show that low-fluence rate PDT is very efficient at inducing apoptotic cell death, whereas neither high-fluence rate PDT nor ionizing radiation produces significant apoptosis. Although the mechanisms remain to be elucidated, the data imply that the observed synergism is likely not due to gamma-induced cell cycle arrest or to PDT-induced inhibition of DNA repair.
Madsen
Steen J
SJ
steenm@ccmail.nevada.edu
Sun
Chung-Ho
CH
Tromberg
Bruce J
BJ
Yeh
Alvin T
AT
Sanchez
Rogelio
R
Hirschberg
Henry
H
D001932:Brain Neoplasms / Q000473:pathology*; D005720:Gamma Rays; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D008954:Models, Biological; D010778:Photochemotherapy; D014407:Tumor Cells, Cultured