{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T11:18:36Z","timestamp":1777979916718,"version":"3.51.4"},"reference-count":52,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"crossref","award":["22-15-00169"],"award-info":[{"award-number":["22-15-00169"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Understanding the molecular mechanisms of carcinogenesis, including disruptions in the homologous recombination system, is fundamental to understanding malignant transformation. Dysfunction of homologous recombination genes, such as BRCA1 and BRCA2, contributes to genomic instability and the development of more aggressive tumor clones. The use of chemical carcinogens enables the modeling of tumor formation and the monitoring of changes in molecular genetic parameters. This approach is important for understanding how tumor cells adapt to genotoxic stress and for advancing the development of personalized cancer therapies. The objective of this study was to evaluate the expression of key homologous recombination system genes in a model of chemically induced carcinogenesis in mice. Materials and Methods: Male outbred ICR (CD-1) laboratory mice (n = 40) were used to study chemically induced carcinogenesis. The animals were divided into four groups: two control groups and two experimental groups, which received 3-methylcholanthrene (MC) or trichloroacetic acid (TCA). Tumor cells were identified by histological analysis of autopsy material using light microscopy after standard hematoxylin and eosin staining. RNA and DNA were extracted from cell suspensions using the RNeasy Plus Mini Kit and QIAamp DNA Mini Kit (Qiagen, Hilden, Germany), respectively. The expression levels of homologous recombination genes were assessed by RT-PCR and microarray analysis. Digital PCR was performed to assess chromosomal aberrations in the Brca1 gene. Results: Tumor formations were identified in laboratory animals two months after 3-methylcholanthrene. Histological analysis revealed morphological changes in a pleomorphic cell tumor, forming diverse, multidirectional fascicular and swirling structures, as well as large solid foci composed of markedly polymorphic spindle-shaped and epithelioid cells. Analysis of copy number aberrations in the examined samples showed that the frequency of Brca1 deletions was 60%, while 40% of animals had normal gene copy number. To further characterize the molecular changes, we assessed gene expression levels through expression microarray analysis. A total of 14 genes were hypoexpressed in the tumor compared to the normal tissue, with p &lt; 0.05. A high level of differential expression was characteristic for Rad50, Rad51, Brca1, Brca2, and Pold4. Two genes, Rad52 and Bard1, exhibited increased expression levels. It was shown that as the tumor mass increased, so did the frequency of homologous recombination genes with hypoexpression. Conclusions: Our findings confirm that MC and TCA influence tumor formation and reveal that suppression of homologous recombination genes may contribute to this process. In addition, it has been established that as tumors progress, the expression of DNA repair genes declines and aberrant gene states accumulate. These data emphasize the importance of studying the state of DNA repair genes for the development of more effective strategies for cancer diagnosis and therapy.<\/jats:p>","DOI":"10.3390\/cimb48030275","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T13:11:36Z","timestamp":1772629896000},"page":"275","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Assessment of Homologous Recombination System Gene Expression in Chemologically Induced Carcinogenesis In Vivo Models"],"prefix":"10.3390","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7419-4512","authenticated-orcid":false,"given":"Matvey M.","family":"Tsyganov","sequence":"first","affiliation":[{"name":"Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, St. Kooperativny 5, Tomsk 634009, Russia"},{"name":"Biochemistry and Molecular Biology Division, Siberian State Medical University, 2 Moskovsky Trakt, Tomsk 634050, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danna Zh.","family":"Bulatova","sequence":"additional","affiliation":[{"name":"Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, St. Kooperativny 5, Tomsk 634009, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3297-1680","authenticated-orcid":false,"given":"Anastasia A.","family":"Fedorenko","sequence":"additional","affiliation":[{"name":"Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, St. Kooperativny 5, Tomsk 634009, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dmitry M.","family":"Loos","sequence":"additional","affiliation":[{"name":"Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, St. Kooperativny 5, Tomsk 634009, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pavel E.","family":"Nikiforov","sequence":"additional","affiliation":[{"name":"Goldberg Research Institute of Pharmacology and Regenerative Medicine, 3 Lenin Avenue, Tomsk 634028, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2716-3075","authenticated-orcid":false,"given":"Irina A.","family":"Tsydenova","sequence":"additional","affiliation":[{"name":"Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, St. Kooperativny 5, Tomsk 634009, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aigerim A.","family":"Bayanbayeva","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology Division, Siberian State Medical University, 2 Moskovsky Trakt, Tomsk 634050, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhansaya","family":"Sharipkhanova","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology Division, Siberian State Medical University, 2 Moskovsky Trakt, Tomsk 634050, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofia S.","family":"Timoshenko","sequence":"additional","affiliation":[{"name":"Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, St. Kooperativny 5, Tomsk 634009, Russia"},{"name":"Biochemistry and Molecular Biology Division, Siberian State Medical University, 2 Moskovsky Trakt, Tomsk 634050, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina K.","family":"Ibragimova","sequence":"additional","affiliation":[{"name":"Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, St. Kooperativny 5, Tomsk 634009, Russia"},{"name":"Biochemistry and Molecular Biology Division, Siberian State Medical University, 2 Moskovsky Trakt, Tomsk 634050, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1158\/1055-9965.EPI-19-1346","article-title":"The key characteristics of carcinogens: Relationship to the hallmarks of cancer, relevant biomarkers, and assays to measure them","volume":"29","author":"Smith","year":"2020","journal-title":"Cancer Epidemiol. 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