title: Low-dose hypersensitivity and bystander effect are not mutually exclusive in A549 lung carcinoma cells after irradiation with charged particles.
abstract: The purpose of this study was to measure survival fraction of A549 lung carcinoma cells irradiated with charged particles of various LET and to determine mechanisms responsible for enhanced cell killing in the low-dose region. A549 cells were irradiated with a broadbeam of either 10 and 25 keV/μm protons or 100 keV/μm alpha particles and then processed for clonogenic assays and phospho-histone H3 staining. The survival fraction of unirradiated A549 cells co-cultured with irradiated cells was also evaluated. A549 cells were shown to exhibit low-dose hypersensitivity (HRS) for both protons and alpha particles. The dose threshold at which HRS occurs decreased with increasing linear energy transfer (LET), whereas αs, the initial survival curve slope, increased with increasing LET. In addition, the enhanced cell killing observed after irradiation with alpha particles was partly attributed to the bystander effect, due to the low proportion of hit cells at very low doses. Co-culture experiments suggest a gap junction-mediated bystander signal. Our results indicate that HRS is likely to be dependent on LET, and that a bystander effect and low-dose hypersensitivity may co-exist within a given cell line.
authors.affiliation: a NAmur Research Institute for LIfe Sciences (NARILIS), Research Center for the Physics of Matter and Radiation (PMR), University of Namur:
authors.forename: Anne-Catherine
authors.initials: AC
authors.lastname: Heuskin
authors.forename: Anne-Catherine
authors.initials: AC
authors.lastname: Wéra
authors.forename: Hélène
authors.initials: H
authors.lastname: Riquier
authors.forename: Carine
authors.initials: C
authors.lastname: Michiels
authors.forename: Stephane
authors.initials: S
authors.lastname: Lucas
mesh_terms: D000512:Alpha Particles; D024201:Bystander Effect; D002277:Carcinoma / Q000473:pathology* / Q000532:radiotherapy; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D006657:Histones / Q000737:chemistry; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics* / Q000473:pathology; D018499:Linear Energy Transfer; D008175:Lung Neoplasms / Q000473:pathology* / Q000532:radiotherapy; D011522:Protons; D011829:Radiation Dosage; D013194:Staining and Labeling
chemical_list: D006657:Histones; D011522:Protons