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High SPF sunscreen prevents erythema but can lead to overexposure to UVA and VL, with unknown consequences. To explore the impact of chronic blue light exposure, we irradiated (50\u2009J\/cm<jats:sup>2<\/jats:sup>, \u03bb\u2009=\u2009408\u2009nm, three times a week) human immortalized keratinocytes under acute (3 irradiations), intermediate (14 irradiations), and chronic (42 irradiations) blue light exposure, monitoring phenotypic and gene expression changes. Chronically exposed keratinocytes exhibit increased nuclei area, chromatin alterations, higher proliferation, and apoptosis resistance, mirroring the consequences of chronic UVA exposure. While acute exposure upregulated keratinization and downregulated tissue repair and apoptosis genes, chronically exposed cells had upregulated genes involved in energy metabolism and oxidative phosphorylation, and downregulated genes were enriched for immune and inflammatory responses. Specific transcription factors were identified in both the acute and chronic stages, some of which have been associated with UVB exposure. <jats:italic>IRF1<\/jats:italic>, <jats:italic>EGR1<\/jats:italic>, <jats:italic>ELF3<\/jats:italic>, <jats:italic>FOSL1<\/jats:italic>, and <jats:italic>CENPX<\/jats:italic>, <jats:italic>SRF<\/jats:italic>, <jats:italic>CEBPB<\/jats:italic>, <jats:italic>KLF4<\/jats:italic> were identified in the acute and chronic stages, respectively. We identified some changes in chronically irradiated keratinocytes similar to malignant transformation, emphasizing the need for further research on the long\u2010term impacts of blue light exposure on human skin.<\/jats:p>","DOI":"10.1111\/php.14095","type":"journal-article","created":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T07:53:16Z","timestamp":1744012396000},"page":"947-959","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Stage\u2010specific phenotypic and transcriptional alterations in <scp>HaCaT<\/scp> keratinocytes exposed to acute and chronic blue light"],"prefix":"10.1111","volume":"101","author":[{"given":"Paulo Newton","family":"Tonolli","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Institute of Chemistry University of Sao Paulo  Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suely Kazue Nagahashi","family":"Marie","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Biology, Department of Neurology, LIM15, Faculdade de Medicina FMUSP Universidade de Sao Paulo  Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sueli Mieko","family":"Oba\u2010Shinjo","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Biology, Department of Neurology, LIM15, Faculdade de Medicina FMUSP Universidade de Sao Paulo  Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5209-0835","authenticated-orcid":false,"given":"Leonardo Vinicius Monteiro","family":"de Assis","sequence":"additional","affiliation":[{"name":"Institute of Neurobiology, Center of Brain Behavior &amp; Metabolism University of L\u00fcbeck  L\u00fcbeck Germany"},{"name":"University Hospital Schleswig\u2010Holstein  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7079-7666","authenticated-orcid":false,"given":"Maur\u00edcio S.","family":"Baptista","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Institute of Chemistry University of Sao Paulo  Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,7]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jphotochemrev.2021.100403"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-4632.2010.04474.x"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.22176"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.2c04424"},{"key":"e_1_2_11_6_1","first-page":"1","article-title":"Sunlight, ultraviolet radiation, vitamin D and skin cancer: how much sunlight do we need?","volume":"810","author":"Holick 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