title: Combined treatment with X-ray irradiation and 5-aminolevulinic acid elicits better transcriptomic response of cell cycle-related factors than X-ray irradiation alone.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors: a Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology , Tsukuba , Ibaraki , Japan.
authors: Junko
authors: J
authors: Takahashi
authors: b Human Technology Research Institute, National Institute of Advanced Industrial Science and Technology , Tsukuba , Ibaraki , Japan.
authors: Masaki
authors: M
authors: Misawa
authors: c Faculty of Applied Biological Sciences , Gifu University , Gifu , Japan.
authors: Hitoshi
authors: H
authors: Iwahashi
mesh_terms: D000622:Aminolevulinic Acid / Q000008:administration & dosage*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002453:Cell Cycle / Q000187:drug effects* / Q000528:radiation effects*; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D010778:Photochemotherapy / Q000379:methods; D011836:Radiation Tolerance / Q000187:drug effects / Q000528:radiation effects; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage; D059467:Transcriptome / Q000528:radiation effects*; D014965:X-Rays
chemical_list: D018797:Cell Cycle Proteins; D011838:Radiation-Sensitizing Agents; D000622:Aminolevulinic Acid
keywords: 5-aminolevulinic acid (ALA); Radiotherapy; X-ray; mouse caner model; protpporphyrin IX (PpIX); sensitizer