{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T05:00:13Z","timestamp":1785214813331,"version":"3.55.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>We used the non-tumorigenic MCF10A and triple-negative MDA-MB-231 breast cell lines to compare cell response to CONV and FLASH dose-rates under normoxic conditions. Beyond evaluating cell survival and DNA\/microtubule damage, we assessed transcriptomic and immunological profiles to describe putative molecular changes. Oxidative stress induced by two different irradiation modalities was also investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Breast cell lines were irradiated with electron beams at increasing doses of 2, 4, 6, 9, 11, and 15 Gy delivered at either FLASH (230 Gy\/s) or CONV (6 Gy\/min) dose rates. Survival fractions were determined by clonogenic assay and dose-response curves. DNA damage was quantified by \u03b3-H2AX and 53BP1 foci counting at 0.5, 1, and 24 hours after treatment with 2 and 5 Gy, while microtubule damage was evaluated by confocal microscopy. Transcriptomic profiling was performed by RNA sequencing 24 hours after RT with doses of 9 and 15 Gy. Immunological profiles were analyzed by using Luminex technique at 24, 48, and 72 hours post-RT. The GSH\/GSSG ratio was also measured by mass spectrometry at 24 hours post-treatments to assess differences in cellular oxidative status.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Cell survival was comparable between FLASH and CONV regimens in both cell lines. However, a dose-rate effect was observed at the level of early DNA damage, with increased \u03b3-H2AX foci 1 hour after FLASH-RT in both cell lines, and greater persistence of 53BP1 foci at 24 hours in MDA-MB-231 cells, suggesting a dose-dependent response. Immunological profiling showed no qualitative differences between dose rates; nevertheless, MDA-MB-231 cells produced higher levels of several factors after FLASH-RT, whereas MCF10A cells displayed minimal variation. Transcriptomic profiling revealed a broader gene modulation following FLASH-RT, with mitochondrial gene upregulation in MCF10A cells and induction of structural genes in MDA-MB-231 cells. No significant differences in glutathione balance were detected between FLASH and CONV irradiation in either breast cell line.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Our findings provide new insights into the early biological responses to ultra-high dose rates\n                      <jats:italic>in vitro<\/jats:italic>\n                      under normoxic conditions, suggesting that the dose-rate effect may influence early cellular processes at different levels, without directly affecting cell survival.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1857611","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T04:26:15Z","timestamp":1785212775000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Early molecular changes induced by FLASH irradiation in MCF10A and MDA-MB-231 breast cell lines"],"prefix":"10.3389","volume":"16","author":[{"given":"Luigi","family":"Minafra","sequence":"first","affiliation":[{"name":"Institute of Bioimaging and Complex Biological Systems (IBSBC)- National Research Council (CNR)","place":["Cefal\u00f9, Italy"]},{"name":"National Institute for Nuclear Physics, Laboratori Nazionali del Sud","place":["Catania, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Calvaruso","sequence":"additional","affiliation":[{"name":"Institute of Bioimaging and Complex Biological Systems (IBSBC)- National Research Council (CNR)","place":["Cefal\u00f9, Italy"]},{"name":"National Institute for Nuclear Physics, Laboratori Nazionali del Sud","place":["Catania, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaia","family":"Pucci","sequence":"additional","affiliation":[{"name":"Institute of Bioimaging and Complex Biological Systems (IBSBC)- National Research Council (CNR)","place":["Cefal\u00f9, Italy"]},{"name":"National Institute for Nuclear Physics, Laboratori Nazionali del Sud","place":["Catania, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Sarnari","sequence":"additional","affiliation":[{"name":"Institute of Bioimaging and Complex Biological Systems (IBSBC)- National Research Council (CNR)","place":["Cefal\u00f9, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Russo","sequence":"additional","affiliation":[{"name":"Institute of Bioimaging and Complex Biological Systems (IBSBC)- National Research Council (CNR)","place":["Cefal\u00f9, Italy"]},{"name":"National Institute for Nuclear Physics, Laboratori Nazionali del Sud","place":["Catania, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Bravat\u00e0","sequence":"additional","affiliation":[{"name":"Institute of Bioimaging and Complex Biological Systems (IBSBC)- National Research Council (CNR)","place":["Cefal\u00f9, Italy"]},{"name":"National Institute for Nuclear Physics, Laboratori Nazionali del Sud","place":["Catania, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco Paolo","family":"Cammarata","sequence":"additional","affiliation":[{"name":"Institute of Bioimaging and Complex Biological Systems (IBSBC)- National Research Council (CNR)","place":["Cefal\u00f9, Italy"]},{"name":"National Institute for Nuclear Physics, Laboratori Nazionali del Sud","place":["Catania, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Di Martino","sequence":"additional","affiliation":[{"name":"Azienda ospedaliero-universitaria pisana (AOUP), U.O. 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