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For this study, human bronchial epithelial BEAS-2B cells were continuously exposed to PET-NPLs for over 20 weeks, after which elevated basal DNA genotoxic damage was observed, as assessed by the alkaline comet assay. In addition, a broad transcriptional suppression of the DDR, with 27 of 84 profiled genes involved in DDR showing reduced expression relative to passage-matched control was observed. The suppressed genes span ATM\/ATR checkpoint signaling, homologous recombination (HR), base excision repair (BER), nucleotide excision repair (NER), and apoptotic pathways. To determine whether chronic PET-NPL exposure altered susceptibility to acute genotoxic challenge in a damage-type-specific manner, cells were treated with methyl methanesulfonate (MMS), ultraviolet-C (UV-C) radiation, or bleomycin. While MMS and UV-C induced comparable levels of DNA damage in control and PET-exposed cells, bleomycin produced significantly greater damage in PET-exposed cells, indicating selective sensitization to doble-strand breaks (DSB)-type and oxidative genotoxic insults. Transcriptional profiling during bleomycin challenge identified 18 DDR genes with relatively higher expression in PET-exposed cells compared to passage-matched controls, encompassing HR, BER, ATM\/ATR signaling, the Fanconi anemia pathway, and apoptosis. Furthermore, PET-exposed cells retained significantly higher residual DNA damage after 3 h of bleomycin challenge, indicating a persistent early repair deficit. Together, these findings suggest that chronic PET-NPL exposure specifically compromises the bronchial epithelial DDR, with potential implications for long-term genomic stability in respiratory epithelia subjected to nanoplastic inhalation.<\/jats:p>","DOI":"10.3390\/ijms27115031","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T12:45:08Z","timestamp":1780404308000},"page":"5031","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Long-Term PET-Nanoplastic Exposure Alters DNA Damage Response Capacity in BEAS-2B Human Bronchial Epithelial Cells"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9620-2069","authenticated-orcid":false,"given":"Michelle","family":"Morataya-Reyes","sequence":"first","affiliation":[{"name":"Group of Mutagenesis, Department of Genetics and Microbiology, Faculty of Biosciences, Universitat Aut\u00f2noma de Barcelona, 08193 Cerdanyola del Vall\u00e8s, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aliro","family":"Villacorta","sequence":"additional","affiliation":[{"name":"Group of Mutagenesis, Department of Genetics and Microbiology, Faculty of Biosciences, Universitat Aut\u00f2noma de Barcelona, 08193 Cerdanyola del Vall\u00e8s, Spain"},{"name":"Facultad de Recursos Naturales Renovables, Universidad Arturo Prat, Iquique 1100000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6201-4112","authenticated-orcid":false,"given":"Raquel","family":"Egea","sequence":"additional","affiliation":[{"name":"Group of Mutagenesis, Department of Genetics and Microbiology, Faculty of Biosciences, Universitat Aut\u00f2noma de Barcelona, 08193 Cerdanyola del Vall\u00e8s, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan","family":"Mart\u00edn-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Group of Mutagenesis, Department of Genetics and Microbiology, Faculty of Biosciences, Universitat Aut\u00f2noma de Barcelona, 08193 Cerdanyola del Vall\u00e8s, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7376-8933","authenticated-orcid":false,"given":"Javier","family":"Guti\u00e9rrez-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Group of Mutagenesis, Department of Genetics and Microbiology, Faculty of Biosciences, Universitat Aut\u00f2noma de Barcelona, 08193 Cerdanyola del Vall\u00e8s, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2454-5163","authenticated-orcid":false,"given":"Susana","family":"Pastor","sequence":"additional","affiliation":[{"name":"Group of Mutagenesis, Department of Genetics and Microbiology, Faculty of Biosciences, Universitat Aut\u00f2noma de Barcelona, 08193 Cerdanyola del Vall\u00e8s, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7891-357X","authenticated-orcid":false,"given":"Ricard","family":"Marcos","sequence":"additional","affiliation":[{"name":"Group of Mutagenesis, Department of Genetics and Microbiology, Faculty of Biosciences, Universitat Aut\u00f2noma de Barcelona, 08193 Cerdanyola del Vall\u00e8s, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6938-1233","authenticated-orcid":false,"given":"Alba","family":"Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Group of Mutagenesis, Department of Genetics and Microbiology, Faculty of Biosciences, Universitat Aut\u00f2noma de Barcelona, 08193 Cerdanyola del Vall\u00e8s, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Alqahtani, S., Alqahtani, S., Saquib, Q., and Mohiddin, F. 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