Microcystin-LR (MC-LR), involved in human and animal poisonings by cyanobacteria, has been shown to be both a potent tumour promoter in rat liver and an inhibitor of serine/threonine protein phosphatases, specifically PP1 and PP2A. The research on the genotoxic potential of MC-LR counts only few in vivo studies. In order to determine the target organs for DNA-damage induction by MC-LR, the single-cell gel electrophoresis (SCGE) or comet assay was performed in mice. Following a single oral administration of 2 and 4mg/kg bw of MC-LR, a statistically significant induction of DNA damage in blood cells was obtained after 3h. However, after an intra-peritoneal injection (ip), DNA lesions were mainly induced in the liver, but were also reported in the kidney, the intestine and the colon. The sensitivity of the ip route compared to the oral route suggested a difference in the bio-disponibility of the toxin. In any case, DNA damage was induced by MC-LR irrespective of the administration route. Among the target organs, the DNA damage induced in the intestinal tissues (ileum and colon) may contribute to an increased cancer risk.
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http://dx.doi.org/10.1016/j.mrgentox.2007.10.024 | DOI Listing |
JCO Precis Oncol
January 2025
Karmanos Cancer Institute and Department of Oncology, Wayne State University School of Medicine, Detroit, MI.
Purpose: Although lung cancer is one of the most common malignancies, the underlying genetics regarding susceptibility remain poorly understood. We characterized the spectrum of pathogenic/likely pathogenic (P/LP) germline variants within DNA damage response (DDR) genes among lung cancer cases and controls in non-Hispanic Whites (NHWs) and African Americans (AAs).
Materials And Methods: Rare, germline variants in 67 DDR genes with evidence of pathogenicity were identified using the ClinVar database.
STAR Protoc
January 2025
Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, 38123 Trento, TN, Italy; Department of Medicine, NYU Langone Medical Center, New York, NY 10016, USA. Electronic address:
Reduced expression of nucleolar genes induces stress and DNA damage. Here, we present a protocol to analyze DNA fragmentation at the single-cell level in Drosophila imaginal discs using an optimized alkaline comet assay. We describe steps for larvae development, tissue disaggregation, and single-cell dissociation.
View Article and Find Full Text PDFBiol Cell
January 2025
Centre de Recherche en Biologie cellulaire de Montpellier (CRBM), Université de Montpellier, Centre National de la Recherche Scientifique, Montpellier, France.
One widespread technique to assess in relative terms the amount of broken DNA present in the genome of individual cells consists of immobilizing the cell's nucleus under an agarose pad (called the nucleoid) and subjecting the whole genome to electrophoresis to force broken DNA molecules out of it. Since the migrating broken DNA molecules create a tail behind the nucleoid, this technique is named the comet assay. While performing comet assays regularly, we systematically observed circular regions devoid of DNA within the nucleoid region.
View Article and Find Full Text PDFFASEB J
January 2025
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Surgery IV, Peking University Cancer Hospital & Institute, Beijing, China.
Chemoresistance is an ongoing challenge for colorectal cancer (CRC) that significantly compromises the anti-tumor efficacy of current drugs. Identifying effective targets or drugs for overcoming chemoresistance is urgently needed. Our previous study showed that WFDC3 served as a tumor suppressor that hindered CRC metastasis.
View Article and Find Full Text PDFActa Parasitol
January 2025
División de Investigación, Facultad de Medicina, Unidad de Investigación UNAM-INC, Universidad Nacional Autónoma de México, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No. 1, Col. Sección XVI, Ciudad de México, C.P. 14080, México.
Leishmania spp. cause a wide range of human diseases, localized skin lesions, mucocutaneous and visceral infections. In the present study, the aim was to investigate the potential role of sanguinarine as a specific inhibitor of Leishmania PP2C that can induce apoptosis in the parasite.
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