Dose and time dependent apoptotic response in a human melanoma cell line exposed to accelerated boron ions at four different LET
2005 (English)In: International Journal of Radiation Biology, ISSN 0955-3002, Vol. 81, no 4, 261-72 p.Article in journal (Refereed) Published
The aim was to investigate and compare the influence of linear energy transfer (LET), dose and time on the induction of apoptosis in a human melanoma cell line exposed to accelerated light boron ((10)B) ions and photons. Cells were exposed in vitro to doses up to 6 Gy accelerated boron ions (40, 80, 125 and 160 eV nm(-1)) and up to 12 Gy photons (0.2 eV nm(-1)). The induction of apoptosis was measured up to 9 days after irradiation using morphological characterization of apoptotic cells and bodies. In parallel, measurements of cell-cycle distribution, monitored by DNA flow cytometry, and cell survival based on the clonogenic cell survival assay, were performed. In addition, the induction and repair of DNA double-strand breaks (DSB), using pulsed-field gel electrophoresis (PFGE) were studied. Accelerated boron ions induced a significant increase in apoptosis as compared with photons at all time points studied. At 1-5 h the percentage of radiation-induced apoptotic cells increased with both dose and LET. At the later time points (24-216 h) the apoptotic response was more complex and did not increase in a strictly LET-dependent manner. The early premitotic apoptotic cells disappeared at 24 h following exposure to the highest LET (160 eV nm(-1)). A postmitotic apoptotic response was seen after release of the dose-, time- and LET-dependent G2/M accumulations. The loss of clonogenic ability was dose- and LET-dependent and the fraction of un-rejoined DSB increased with increasing LET. Despite the LET-dependent clonogenic cell killing, it was not possible to measure quantitatively a LET-dependent apoptotic response. This was due to the different time course of appearance and disappearance of apoptotic cells.
Place, publisher, year, edition, pages
2005. Vol. 81, no 4, 261-72 p.
Apoptosis, Boron/*therapeutic use, Cell Division/radiation effects, Cell Line; Tumor, Cell Survival/radiation effects, DNA Damage, DNA Repair, G2 Phase/radiation effects, Humans, Linear Energy Transfer, Melanoma/pathology/*radiotherapy, Research Support; Non-U.S. Gov't
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-75375DOI: 10.1080/09553000500141215PubMedID: 16019936OAI: oai:DiVA.org:uu-75375DiVA: diva2:103285