title: The different radiation response and radiation-induced bystander effects in colorectal carcinoma cells differing in p53 status.
abstract: Radiation-induced bystander effect, appearing as different biological changes in cells that are not directly exposed to ionizing radiation but are under the influence of molecular signals secreted by irradiated neighbors, have recently attracted considerable interest due to their possible implication for radiotherapy. However, various cells present diverse radiosensitivity and bystander responses that depend, inter alia, on genetic status including TP53, the gene controlling the cell cycle, DNA repair and apoptosis. Here we compared the ionizing radiation and bystander responses of human colorectal carcinoma HCT116 cells with wild type or knockout TP53 using a transwell co-culture system. The viability of exposed to X-rays (0-8 Gy) and bystander cells of both lines showed a roughly comparable decline with increasing dose. The frequency of micronuclei was also comparable at lower doses but at higher increased considerably, especially in bystander TP53-/- cells. Moreover, the TP53-/- cells showed a significantly elevated frequency of apoptosis, while TP53+/+ counterparts expressed high level of senescence. The cross-matched experiments where irradiated cells of one line were co-cultured with non-irradiated cells of opposite line show that both cell lines were also able to induce bystander effects in their counterparts, however different endpoints revealed with different strength. Potential mediators of bystander effects, IL-6 and IL-8, were also generated differently in both lines. The knockout cells secreted IL-6 at lower doses whereas wild type cells only at higher doses. Secretion of IL-8 by TP53-/- control cells was many times lower than that by TP53+/+ but increased significantly after irradiation. Transcription of the NFκBIA was induced in irradiated TP53+/+ mainly, but in bystanders a higher level was observed in TP53-/- cells, suggesting that TP53 is required for induction of NFκB pathway after irradiation but another mechanism of activation must operate in bystander cells.
authors.affiliation: Biosystems Group, Institute of Automatic Control, Silesian University of Technology, 16 Akademicka Street, 44-100 Gliwice, Poland. Electronic address: maria.widel@polsl.pl.
authors.forename: Maria
authors.initials: M
authors.lastname: Widel
authors.affiliation: Biosystems Group, Institute of Automatic Control, Silesian University of Technology, 16 Akademicka Street, 44-100 Gliwice, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Lalik
authors.affiliation: Biosystems Group, Institute of Automatic Control, Silesian University of Technology, 16 Akademicka Street, 44-100 Gliwice, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Krzywon
authors.affiliation: College of Inter-faculty Individual Studies in Mathematics and Natural Sciences, University of Warsaw, 93 Zwirki i Wigury Street, 02-089 Warsaw, Poland; Department of Integrated Mathematical Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Poleszczuk
authors.affiliation: Biosystems Group, Institute of Automatic Control, Silesian University of Technology, 16 Akademicka Street, 44-100 Gliwice, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Fujarewicz
authors.affiliation: Biosystems Group, Institute of Automatic Control, Silesian University of Technology, 16 Akademicka Street, 44-100 Gliwice, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Rzeszowska-Wolny
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects*; D024201:Bystander Effect / Q000528:radiation effects; D045744:Cell Line, Tumor / Q000528:radiation effects; D016922:Cellular Senescence / Q000528:radiation effects; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D016158:Genes, p53; D006801:Humans; D020672:I-kappa B Proteins / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D015162:Micronucleus Tests; D000072000:NF-KappaB Inhibitor alpha; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
chemical_list: D020672:I-kappa B Proteins; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; C000606204:NFKBIA protein, human; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016159:Tumor Suppressor Protein p53; D000072000:NF-KappaB Inhibitor alpha
keywords: Apoptosis; Colon carcinoma cells differing in TP53 status; NFκB pathway; Premature senescence; Pro-inflammatory cytokines IL-6 and IL-8; Radiation-induced bystander effect