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

Junko Takahashi*, Masaki Misawa, Hitoshi Iwahashi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)774-789
Number of pages16
JournalInternational Journal of Radiation Biology
Volume92
Issue number12
DOIs
Publication statusPublished - 2016 Dec 1
Externally publishedYes

Keywords

  • 5-aminolevulinic acid (ALA)
  • Radiotherapy
  • X-ray
  • mouse caner model
  • protpporphyrin IX (PpIX)
  • sensitizer

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging

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