title: Comparison of human lung cancer cell radiosensitivity after irradiations with therapeutic protons and carbon ions.
abstract: The aim of this study was to investigate effects of irradiations with the therapeutic proton and carbon ion beams in two non-small cell lung cancers, CRL5876 adenocarcinoma and HTB177 large cell lung carcinoma. The DNA damage response dynamics, cell cycle regulation, and cell death pathway activation were followed. Viability of both cell lines was lower after carbon ions compared to the therapeutic proton irradiations. HTB177 cells showed higher recovery than CRL5876 cells seven days following the treatments, but the survival rates of both cell lines were lower after exposure to carbon ions with respect to therapeutic protons. When analyzing cell cycle distribution of both CRL5876 and HTB177 cells, it was noticed that therapeutic protons predominantly induced G1 arrest, while the cells after carbon ions were arrested in G2/M phase. The results illustrated that differences in the levels of phosphorylated H2AX, a double-strand break marker, exist after therapeutic proton and carbon ion irradiations. We also observed dose- and time-dependent increase in the p53 and p21 levels after applied irradiations. Carbon ions caused larger increase in the quantity of p53 and p21 compared to therapeutic protons. These results suggested that various repair mechanisms were induced in the treated cells. Considering the fact that we have not observed any distinct change in the Bax/Bcl-2 ratio following irradiations, it seemed that different types of cell death were involved in the response to the two types of irradiations that were applied.
authors.affiliation: 1 Vinča Institute of Nuclear Sciences, University of Belgrade, Belgrade 11001, Serbia.
authors.forename: Otilija D
authors.initials: OD
authors.lastname: Keta
authors.affiliation: 2 Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34000, Serbia.
authors.forename: Danijela V
authors.initials: DV
authors.lastname: Todorović
authors.affiliation: 1 Vinča Institute of Nuclear Sciences, University of Belgrade, Belgrade 11001, Serbia.
authors.forename: Tanja M
authors.initials: TM
authors.lastname: Bulat
authors.affiliation: 3 Laboratori Nazionali del Sud, Instituto Nazionale di Fisica Nucleare, Catania 95123, Italy.
authors.forename: Pablo Ga
authors.initials: PG
authors.lastname: Cirrone
authors.affiliation: 3 Laboratori Nazionali del Sud, Instituto Nazionale di Fisica Nucleare, Catania 95123, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Romano
authors.affiliation: 3 Laboratori Nazionali del Sud, Instituto Nazionale di Fisica Nucleare, Catania 95123, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Cuttone
authors.affiliation: 1 Vinča Institute of Nuclear Sciences, University of Belgrade, Belgrade 11001, Serbia.
authors.forename: Ivan M
authors.initials: IM
authors.lastname: Petrović
authors.affiliation: 1 Vinča Institute of Nuclear Sciences, University of Belgrade, Belgrade 11001, Serbia.
authors.forename: Aleksandra M
authors.initials: AM
authors.lastname: Ristić Fira
mesh_terms: D002244:Carbon / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000528:radiation effects; D045744:Cell Line, Tumor / Q000528:radiation effects*; D002470:Cell Survival / Q000528:radiation effects; D004249:DNA Damage / Q000528:radiation effects; D004260:DNA Repair; D006801:Humans; D007477:Ions / Q000494:pharmacology*; D011522:Protons; D011836:Radiation Tolerance
chemical_list: D007477:Ions; D011522:Protons; D002244:Carbon
keywords: DNA damage; Lung cancer; carbon ions; cell irradiation; protons; radiobiology