{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T04:06:13Z","timestamp":1780459573620,"version":"3.54.1"},"reference-count":56,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Doxorubicin (Dox) is a cornerstone in the treatment of pediatric acute lymphoblastic leukemia (ALL), but its use is limited by dose-dependent cardiotoxicity. Oxidative stress, arising from mitochondrial dysfunction, enzymatic generation of reactive oxygen species, and cardiotoxic metabolites, has been implicated as a central mechanism, with interindividual variability partly influenced by genetic factors. This study evaluated oxidative DNA damage 8-hydroxy-2\u2032-deoxyguanosine (8-OHdG) as an integrative marker of redox-related pathways in Dox-induced cardiotoxicity. In a prospective case\u2013control study, 93 pediatric patients with ALL treated with Dox and 63 controls were included. Cardiotoxicity was assessed by serial echocardiography, and 8-OHdG levels were measured by ELISA. Genotyping of ABCC1 rs3743527, NCF4 rs1883112, and CBR3 rs1056892 was performed, and multivariable analyses were conducted. Dox-treated patients showed higher 8-OHdG levels than controls, and patients with cardiotoxicity (n = 11) had higher levels than those without. A higher frequency and severity of cardiotoxicity was observed in female patients, although this finding should be interpreted cautiously. Although allele frequencies did not reach statistical significance, distinct distribution patterns were observed between groups. These findings suggest that 8-OHdG may function as an integrative marker of redox dysfunction associated with Dox-induced cardiotoxicity.<\/jats:p>","DOI":"10.3390\/cimb48060577","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T02:37:26Z","timestamp":1780454246000},"page":"577","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Oxidative DNA Damage as an Integrative Marker of Redox Dysfunction Associated with Doxorubicin-Induced Cardiotoxicity in Pediatric Leukemia"],"prefix":"10.3390","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5927-4992","authenticated-orcid":false,"given":"Jes\u00fas Alonso","family":"G\u00e1ndara-Mireles","sequence":"first","affiliation":[{"name":"CIIDIR-Durango Unit, National Polytechnic Institute, Genomics Academy, Durango 34220, Mexico"},{"name":"Latin American Network for Implementation and Validation of Pharmacogenomic Clinical Guidelines (RELIVAF-CYTED), Santiago 8500000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elio Aar\u00f3n","family":"Reyes Espinoza","sequence":"additional","affiliation":[{"name":"Pediatric Hemato-Oncology Service, State Cancer Center (CECAN), Durango 34000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4158-1078","authenticated-orcid":false,"given":"Ver\u00f3nica","family":"Loera-Casta\u00f1eda","sequence":"additional","affiliation":[{"name":"CIIDIR-Durango Unit, National Polytechnic Institute, Genomics Academy, Durango 34220, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lourdes Patricia","family":"C\u00f3rdova Hurtado","sequence":"additional","affiliation":[{"name":"Pediatric Hemato-Oncology Service, State Cancer Center (CECAN), Durango 34000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio Emilio","family":"Gonz\u00e1lez Font","sequence":"additional","affiliation":[{"name":"Pediatric Service, General Hospital of Durango, Maternal and Child Tower, Durango 34000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio Cesar","family":"Grijalva \u00c1vila","sequence":"additional","affiliation":[{"name":"CIIDIR-Durango Unit, National Polytechnic Institute, Genomics Academy, Durango 34220, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio","family":"Villanueva Fierro","sequence":"additional","affiliation":[{"name":"CIIDIR-Durango Unit, National Polytechnic Institute, Genomics Academy, Durango 34220, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismael","family":"Lares-Asseff","sequence":"additional","affiliation":[{"name":"Latin American Network for Implementation and Validation of Pharmacogenomic Clinical Guidelines (RELIVAF-CYTED), Santiago 8500000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia Mora","family":"Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Epidemiology Service, State Cancer Center (CECAN), Durango 34000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Velasco Villa","sequence":"additional","affiliation":[{"name":"Pediatric Service, General Hospital of Durango, Maternal and Child Tower, Durango 34000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo","family":"Pay\u00e1n G\u00e1ndara","sequence":"additional","affiliation":[{"name":"Epidemiology Service, State Cancer Center (CECAN), Durango 34000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8981-055X","authenticated-orcid":false,"given":"Leslie","family":"Patr\u00f3n-Romero","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Psychology, Autonomous University of Baja California, Tijuana 22390, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Horacio","family":"Almanza-Reyes","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Psychology, Autonomous University of Baja California, Tijuana 22390, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1056\/NEJMra1400972","article-title":"Acute lymphoblastic leukemia in children","volume":"373","author":"Hunger","year":"2015","journal-title":"N. 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