Combined treatment with X-ray irradiation and 5-aminolevulinic acid elicits better transcriptomic response of cell cycle-related factors than X-ray irradiation alone. (1st December 2016)

• Record Type: Journal Article
• Authors: Takahashi, Junko; Misawa, Masaki; Iwahashi, Hitoshi
• Is Part Of: International journal of radiation biology. Volume 92:Number 12(2016:Dec.)
• Page Start: 774
• Page End: 789
• Publication Date: 2016-12-01
• Subjects: Radiotherapy -- X-ray -- sensitizer -- protpporphyrin IX (PpIX) -- 5-aminolevulinic acid (ALA) -- mouse caner model; Radiation -- Physiological effect -- Periodicals; Radiobiology -- Periodicals; 571.45
• DOI: 10.1080/09553002.2016.1230240
• Languages: English
• ISSNs: 0955-3002

Abstract

Abstract: Purpose: 5-Aminolevulinic acid (ALA) is a precursor of the photosensitizer protoporphyrin (PpIX) used in photodynamic therapy. In our previous work, PpIX enhanced the generation of reactive oxygen species by X-ray irradiation. In this study, we evaluated the potential of ALA as an endogenous sensitizer to X-ray irradiation. Methodology: Tumor-bearing C57BL/6J mice implanted with B16-BL6 melanoma cells were subsequently treated with irradiation (3 Gy/day for 10 days; total, 30 Gy) plus local administration of 50 mg/kg ALA 24 hours prior to each irradiation (ALA-XT). Tumor-bearing mice without treatment (NT), those treated with ALA only (ALAT), and those treated with X-ray irradiation only (XT) were used as controls. Results: ALA potentiated tumor suppression by X-ray irradiation. In microarray analyses using tumor tissue collected after 10 sessions of fractional irradiation, functional analysis revealed that the majority of dysregulated genes in the XT and ALA-XT groups were related to cell-cycle arrest. Finally, the XT and ALA-XT groups differed in the strength of expression, but not in the pattern of expression. Conclusions: mRNA analysis revealed that the combined use of ALA and X-ray irradiation sensitized tumors to X-ray treatment. Furthermore, the present results were consistent with ALA's tumor suppressive effects in vivo.