Combined treatment of ionizing radiation and photosensitization by 5-aminolevulinic acid-induced protoporphyrin IX.
The response of human colon adenocarcinoma cells of the line WiDr to the combined treatment of ionizing radiation and photosensitization by 5-aminolevulinic acid-induced protoporphyrin IX was assessed by a colony-forming assay. A dose of X rays inactivating approximately 50% of the cells was used. Seventy to 85% of the cells accumulated in S and G2 + M phase 12-24 h after such a treatment as measured by flow cytometry, while the distribution of cells in the phases of the cell cycle approached that of untreated cells 48 h after X-ray treatment. Cellular photosensitization was developed by endogenous synthesis of protoporphyrin IX (PPIX) from the precursor 5-aminolevulinic acid (5-ALA). This was performed by treating the cells with 1 mM 5-ALA for 4 h in a serum-free medium. The endogenous synthesis of PPIX increased with time after the cells had been subcultured, i.e. the ability of the cells to synthesize PPIX increased 1.5-2-fold within 48 h of incubation. This was not due to effects of trypsin on the cells. Photochemotherapy with 5-ALA was given 0-48 h after X rays. The combined cytotoxic effect was analyzed by an isobologram after correction of the survival curves for microcolony formation and differences in intracellular concentration of PPIX. The results indicate that 5-ALA PCT given 0-4 h after X rays acts slightly antagonistically while 5-ALA PCT given 12-48 h after X rays acts slightly synergistically.
Berg
K
K
Institute for Cancer Research, Department of Biophysics, Montebello, Oslo, Norway.
Luksiene
Z
Z
Moan
J
J
Ma
L
L
D000230:Adenocarcinoma; D000622:Aminolevulinic Acid; D002453:Cell Cycle / Q000187:drug effects* / Q000528:radiation effects; D002455:Cell Division / Q000187:drug effects* / Q000528:radiation effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects; D003110:Colonic Neoplasms; D005434:Flow Cytometry; D016195:G2 Phase; D006801:Humans; D007700:Kinetics; D008027:Light; D011524:Protoporphyrins / Q000494:pharmacology*; D011839:Radiation, Ionizing; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D016196:S Phase; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014965:X-Rays
D011524:Protoporphyrins; D011838:Radiation-Sensitizing Agents; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX