Combined treatment with X-ray irradiation and 5-aminolevulinic acid elicits better transcriptomic response of cell cycle-related factors than X-ray irradiation alone

• Published in: International journal of radiation biology 2016-12, Vol.92 (12), p.774-789
• Main Authors: Takahashi, Junko, Misawa, Masaki, Iwahashi, Hitoshi
• Format: Article
• Language: English
• Subjects: 5-aminolevulinic acid (ALA); Aminolevulinic Acid - administration & dosage; Animals; Apoptosis - drug effects; Apoptosis - radiation effects; Cell Cycle - drug effects; Cell Cycle - radiation effects; Cell Cycle Proteins - metabolism; Cell Line, Tumor; Female; Gene Expression Regulation, Neoplastic - drug effects; Gene Expression Regulation, Neoplastic - radiation effects; Mice; Mice, Inbred C57BL; mouse caner model; Neoplasms, Experimental - drug therapy; Neoplasms, Experimental - metabolism; Neoplasms, Experimental - pathology; Photochemotherapy - methods; protpporphyrin IX (PpIX); Radiation Tolerance - drug effects; Radiation Tolerance - radiation effects; Radiation-Sensitizing Agents - administration & dosage; Radiotherapy; sensitizer; Space life sciences; Transcriptome - radiation effects; X-ray; X-Rays
• ISSN: 0955-3002; 1362-3095
• DOI: 10.1080/09553002.2016.1230240

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.