title: Biological effects of passive versus active scanning proton beams on human lung epithelial cells.
abstract: The goal was to characterize differences in cell response after exposure to active beam scanning (ABS) protons compared to a passive delivery system. Human lung epithelial (HLE) cells were evaluated at various locations along the proton depth dose profile. The dose delivered at the Bragg peak position was essentially identical (∼4 Gy) with the two techniques, but depth dose data showed that ABS resulted in lower doses at entry and more rapid drop-off after the peak. Average dose rates for the passive and ABS beams were 1.1 Gy/min and 5.1 Gy/min, respectively; instantaneous dose rates were 19.2 Gy/min and 2,300 Gy/min (to a 0.5 × 0.5 mm(2) voxel). Analysis of DNA synthesis was based on (3)H-TdR incorporation. Quantitative real-time polymerase chain reaction (RT-PCR) was done to determine expression of genes related to p53 signaling and DNA damage; a total of 152 genes were assessed. Spectral karyotyping and analyses of the Golgi apparatus and cytokines produced by the HLE cells were also performed. At or near the Bragg peak position, ABS protons resulted in a greater decrease in DNA synthesis compared to passively delivered protons. Genes with >2-fold change (P < 0.05 vs. 0 Gy) after passive proton irradiation at one or more locations within the Bragg curve were BTG2, CDKN1A, IFNB1 and SIAH1. In contrast, many more genes had >2-fold difference with ABS protons: BRCA1, BRCA2, CDC25A, CDC25C, CCNB2, CDK1, DMC1, DNMT1, E2F1, EXO1, FEN1, GADD45A, GTSE1, IL-6, JUN, KRAS, MDM4, PRC1, PTTG1, RAD51, RPA1, TNF, WT1, XRCC2, XRCC3 and XRCC6BP1. Spectral karyotyping revealed numerous differences in chromosomal abnormalities between the two delivery systems, especially at or near the Bragg peak. Percentage of cells staining for the Golgi apparatus was low after exposure to passive and active proton beams. Studies such as this are needed to ensure patient safety and make modifications in ABS delivery, if necessary.
authors: Department of Basic Sciences, -Division of Radiation Research, Loma Linda University, Chan Shun Pavilion, Loma Linda, CA 92354, U.S.A. dgridley@llu.edu.
authors: Daila S
authors: DS
authors: Gridley
authors: Department of Basic Sciences, -Division of Radiation Research, Loma Linda University, Chan Shun Pavilion, Loma Linda, CA 92354, U.S.A.
authors: Michael J
authors: MJ
authors: Pecaut
authors: Department of Basic Sciences, -Division of Radiation Research, Loma Linda University, Chan Shun Pavilion, Loma Linda, CA 92354, U.S.A.
authors: Xiao W
authors: XW
authors: Mao
authors: Department of Radiation Medicine, Loma Linda University and Medical Center, Loma Linda, CA, U.S.A.
authors: Andrew J
authors: AJ
authors: Wroe
authors: Department of Basic Sciences, -Division of Radiation Research, Loma Linda University, Chan Shun Pavilion, Loma Linda, CA 92354, U.S.A. Dr. Luo-Owen is currently in Trauma Services at Loma Linda University Medical Center.
authors: Xian
authors: X
authors: Luo-Owen
mesh_terms: D056809:Alveolar Epithelial Cells / Q000378:metabolism / Q000528:radiation effects*; D002869:Chromosome Aberrations / Q000528:radiation effects; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage / Q000235:genetics; D004261:DNA Replication / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000528:radiation effects; D006056:Golgi Apparatus / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D059785:Karyotype; D008875:Middle Aged; D061766:Proton Therapy; D011522:Protons / Q000009:adverse effects*; D011829:Radiation Dosage; D011839:Radiation, Ionizing; D012062:Relative Biological Effectiveness; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D016207:Cytokines; D011522:Protons; D016159:Tumor Suppressor Protein p53
keywords: Chromosome aberrations; DNA synthesis; Gene expression; Ionizing radiation; Spectral karyotyping.; Spot scanning