Cellular and molecular effects of protons: apoptosis induction and potential implications for cancer therapy
Due to their ballistic precision, apoptosis induction by protons could be a strategy to specifically eliminate neoplastic cells. To characterize the cellular and molecular effects of these hadrons, we performed dose-response and time-course experiments by exposing different cell lines (PC3, Ca301D,...
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| Veröffentlicht in: | Apoptosis (London) 2006-01, Vol.11 (1), p.57-66 |
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| creator | Di Pietro, C Piro, S Tabbì, G Ragusa, M Di Pietro, V Zimmitti, V Cuda, F Anello, M Consoli, U Salinaro, E T Caruso, M Vancheri, C Crimi, N Sabini, M G Cirrone, G A P Raffaele, L Privitera, G Pulvirenti, A Giugno, R Ferro, A Cuttone, G Lo Nigro, S Purrello, R Purrello, F Purrello, M |
| description | Due to their ballistic precision, apoptosis induction by protons could be a strategy to specifically eliminate neoplastic cells. To characterize the cellular and molecular effects of these hadrons, we performed dose-response and time-course experiments by exposing different cell lines (PC3, Ca301D, MCF7) to increasing doses of protons and examining them with FACS, RT-PCR, and electron spin resonance (ESR). Irradiation with a dose of 10 Gy of a 26,7 Mev proton beam altered cell structures such as membranes, caused DNA double strand breaks, and significantly increased intracellular levels of hydroxyl ions, are active oxygen species (ROS). This modified the transcriptome of irradiated cells, activated the mitochondrial (intrinsic) pathway of apoptosis, and resulted in cycle arrest at the G2/M boundary. The number of necrotic cells within the irradiated cell population did not significantly increase with respect to the controls. The effects of irradiation with 20 Gy were qualitatively as well as quantitatively similar, but exposure to 40 Gy caused massive necrosis. Similar experiments with photons demonstrated that they induce apoptosis in a significantly lower number of cells and in a temporally delayed manner. These data advance our knowledge on the cellular and molecular effects of proton irradiation and could be useful for improving current hadrontherapy protocols. |
| doi_str_mv | 10.1007/s10495-005-3346-1 |
| format | Article |
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To characterize the cellular and molecular effects of these hadrons, we performed dose-response and time-course experiments by exposing different cell lines (PC3, Ca301D, MCF7) to increasing doses of protons and examining them with FACS, RT-PCR, and electron spin resonance (ESR). Irradiation with a dose of 10 Gy of a 26,7 Mev proton beam altered cell structures such as membranes, caused DNA double strand breaks, and significantly increased intracellular levels of hydroxyl ions, are active oxygen species (ROS). This modified the transcriptome of irradiated cells, activated the mitochondrial (intrinsic) pathway of apoptosis, and resulted in cycle arrest at the G2/M boundary. The number of necrotic cells within the irradiated cell population did not significantly increase with respect to the controls. The effects of irradiation with 20 Gy were qualitatively as well as quantitatively similar, but exposure to 40 Gy caused massive necrosis. Similar experiments with photons demonstrated that they induce apoptosis in a significantly lower number of cells and in a temporally delayed manner. These data advance our knowledge on the cellular and molecular effects of proton irradiation and could be useful for improving current hadrontherapy protocols.</description><identifier>ISSN: 1360-8185</identifier><identifier>EISSN: 1573-675X</identifier><identifier>DOI: 10.1007/s10495-005-3346-1</identifier><identifier>PMID: 16374542</identifier><language>eng</language><publisher>Netherlands: Springer Nature B.V</publisher><subject>Apoptosis ; Apoptosis - genetics ; Apoptosis - radiation effects ; Base Sequence ; Cancer therapies ; Cell Cycle - radiation effects ; Cell Line, Tumor ; DNA Damage ; DNA Primers - genetics ; Electron paramagnetic resonance ; Electron spin ; Electron spin resonance ; Electron Spin Resonance Spectroscopy ; Female ; Flow Cytometry ; Hadrons ; Humans ; Hydroxyl ions ; Intracellular levels ; Irradiation ; Male ; Mitochondria ; Necrosis ; Neoplasms - genetics ; Neoplasms - metabolism ; Neoplasms - pathology ; Neoplasms - radiotherapy ; Photons ; Photons - therapeutic use ; Polymerase chain reaction ; Proton beams ; Proton irradiation ; Protons ; Protons - therapeutic use ; Radiation dosage ; Reactive oxygen species ; Reactive Oxygen Species - metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - genetics ; RNA, Neoplasm - genetics ; Spin resonance ; Transcriptomes</subject><ispartof>Apoptosis (London), 2006-01, Vol.11 (1), p.57-66</ispartof><rights>Springer Science + Business Media, Inc. 2006.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c436t-8f9a3619a7bd2edf9613b0777c4c981dcb73f496b2a2a02c78a645b3666fbdd43</citedby><cites>FETCH-LOGICAL-c436t-8f9a3619a7bd2edf9613b0777c4c981dcb73f496b2a2a02c78a645b3666fbdd43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16374542$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Di Pietro, C</creatorcontrib><creatorcontrib>Piro, S</creatorcontrib><creatorcontrib>Tabbì, G</creatorcontrib><creatorcontrib>Ragusa, M</creatorcontrib><creatorcontrib>Di Pietro, V</creatorcontrib><creatorcontrib>Zimmitti, V</creatorcontrib><creatorcontrib>Cuda, F</creatorcontrib><creatorcontrib>Anello, M</creatorcontrib><creatorcontrib>Consoli, U</creatorcontrib><creatorcontrib>Salinaro, E T</creatorcontrib><creatorcontrib>Caruso, M</creatorcontrib><creatorcontrib>Vancheri, C</creatorcontrib><creatorcontrib>Crimi, N</creatorcontrib><creatorcontrib>Sabini, M G</creatorcontrib><creatorcontrib>Cirrone, G A P</creatorcontrib><creatorcontrib>Raffaele, L</creatorcontrib><creatorcontrib>Privitera, G</creatorcontrib><creatorcontrib>Pulvirenti, A</creatorcontrib><creatorcontrib>Giugno, R</creatorcontrib><creatorcontrib>Ferro, A</creatorcontrib><creatorcontrib>Cuttone, G</creatorcontrib><creatorcontrib>Lo Nigro, S</creatorcontrib><creatorcontrib>Purrello, R</creatorcontrib><creatorcontrib>Purrello, F</creatorcontrib><creatorcontrib>Purrello, M</creatorcontrib><title>Cellular and molecular effects of protons: apoptosis induction and potential implications for cancer therapy</title><title>Apoptosis (London)</title><addtitle>Apoptosis</addtitle><description>Due to their ballistic precision, apoptosis induction by protons could be a strategy to specifically eliminate neoplastic cells. To characterize the cellular and molecular effects of these hadrons, we performed dose-response and time-course experiments by exposing different cell lines (PC3, Ca301D, MCF7) to increasing doses of protons and examining them with FACS, RT-PCR, and electron spin resonance (ESR). Irradiation with a dose of 10 Gy of a 26,7 Mev proton beam altered cell structures such as membranes, caused DNA double strand breaks, and significantly increased intracellular levels of hydroxyl ions, are active oxygen species (ROS). This modified the transcriptome of irradiated cells, activated the mitochondrial (intrinsic) pathway of apoptosis, and resulted in cycle arrest at the G2/M boundary. The number of necrotic cells within the irradiated cell population did not significantly increase with respect to the controls. The effects of irradiation with 20 Gy were qualitatively as well as quantitatively similar, but exposure to 40 Gy caused massive necrosis. Similar experiments with photons demonstrated that they induce apoptosis in a significantly lower number of cells and in a temporally delayed manner. These data advance our knowledge on the cellular and molecular effects of proton irradiation and could be useful for improving current hadrontherapy protocols.</description><subject>Apoptosis</subject><subject>Apoptosis - genetics</subject><subject>Apoptosis - radiation effects</subject><subject>Base Sequence</subject><subject>Cancer therapies</subject><subject>Cell Cycle - radiation effects</subject><subject>Cell Line, Tumor</subject><subject>DNA Damage</subject><subject>DNA Primers - genetics</subject><subject>Electron paramagnetic resonance</subject><subject>Electron spin</subject><subject>Electron spin resonance</subject><subject>Electron Spin Resonance Spectroscopy</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Hadrons</subject><subject>Humans</subject><subject>Hydroxyl ions</subject><subject>Intracellular levels</subject><subject>Irradiation</subject><subject>Male</subject><subject>Mitochondria</subject><subject>Necrosis</subject><subject>Neoplasms - 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| subjects | Apoptosis Apoptosis - genetics Apoptosis - radiation effects Base Sequence Cancer therapies Cell Cycle - radiation effects Cell Line, Tumor DNA Damage DNA Primers - genetics Electron paramagnetic resonance Electron spin Electron spin resonance Electron Spin Resonance Spectroscopy Female Flow Cytometry Hadrons Humans Hydroxyl ions Intracellular levels Irradiation Male Mitochondria Necrosis Neoplasms - genetics Neoplasms - metabolism Neoplasms - pathology Neoplasms - radiotherapy Photons Photons - therapeutic use Polymerase chain reaction Proton beams Proton irradiation Protons Protons - therapeutic use Radiation dosage Reactive oxygen species Reactive Oxygen Species - metabolism Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - genetics RNA, Neoplasm - genetics Spin resonance Transcriptomes |
| title | Cellular and molecular effects of protons: apoptosis induction and potential implications for cancer therapy |
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