The use of radiation therapy is a cornerstone of modern cancer treatment. The number of patients that undergo radiation as a part of their therapy regimen is only increasing every year, but this does not come without cost. As this number increases, so too does the incidence of secondary, radiation-induced neoplasias, creating a need for therapeutic agents targeted specifically towards incidence reduction and treatment of these cancers. Development and efficacy testing of these agents requires not only extensive in vitro testing but also a set of reliable animal models to accurately recreate the complex situations of radiation-induced carcinogenesis. As radiation-induced leukemic progression often involves genomic changes such as rearrangements, deletions, and changes in methylation, the laboratory mouse Mus musculus, with its fully sequenced genome, is a powerful tool in cancer research. This fact, combined with the molecular and physiological similarities it shares with man and its small size and high rate of breeding in captivity, makes it the most relevant model to use in radiation-induced leukemia research. In this work, we review relevant M. musculus inbred and F1 hybrid animal models, as well as methods of induction of radiation-induced myeloid leukemia. Associated molecular pathologies are also included.
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http://dx.doi.org/10.1186/1479-7364-8-13 | DOI Listing |
Int J Radiat Biol
January 2025
Consumer and Clinical Radiation Protection Bureau, Health Canada, Ottawa, ON, Canada.
Background: Recent advancements in omics and benchmark dose (BMD) modeling have facilitated identifying the dose required for a predetermined change in a response (e.g. gene or protein change) that can be used to establish acceptable dose levels for hazardous exposures.
View Article and Find Full Text PDFBiochem Biophys Res Commun
February 2025
Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, China. Electronic address:
Leukopenia, marked by diminished white blood cell (WBC) counts, presents significant challenges in the management of hematological malignancies and immunocompromised patients. This study evaluated the therapeutic potential of miltefosine (MFS), a phospholipid analogue, for treating leukopenia. In vitro studies using HL60 and NB4 cells revealed that MFS effectively promoted neutrophil differentiation and function, evidenced by the upregulation of surface markers CD11b, CD11c, CD14, and CD15, as well as enhanced bactericidal activity assessed through the NBT reduction assay.
View Article and Find Full Text PDFDose Response
December 2024
Canadian Nuclear Laboratories - Retired, Chalk River, ON, Canada.
The Hiroshima/Nagasaki (H/N) studies by the Radiation Effect Research Foundation have not shown increased leukaemia for acute doses below 200 milli-gray (mGy). By contrast the INWORKS study of leukaemia in workers stated: "This study provides strong evidence of positive associations between protracted low-dose radiation exposure and leukemia". The INWORKS study also claimed increased leukaemia, not including Chronic Lymphocytic Leukaemia, at cumulative occupational doses of less than 100 mGy.
View Article and Find Full Text PDFMol Cancer Ther
December 2024
Department of Radiation Oncology, University of Michigan Rogel Cancer Center, Ann Arbor, Michigan.
PARP inhibitors sensitize pancreatic ductal adenocarcinoma (PDAC) to radiation by inducing DNA damage and replication stress. These mechanisms also have the potential to enhance radiation-induced type I interferon (T1IFN)-mediated antitumoral immune responses. We hypothesized that the PARP inhibitor olaparib would also potentiate radiation-induced T1IFN to promote antitumor immune responses and sensitization of otherwise resistant PDAC to immunotherapy.
View Article and Find Full Text PDFCrit Rev Oncol Hematol
December 2024
Pacific Neuroscience Institute, Santa Monica, CA, USA; Department of Translational Neuroscience, Saint John's Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA, USA. Electronic address:
Background: High-grade gliomas are devastating cancers that remain incurable with standard surgical resection and radiochemotherapy. Although beneficial against neoplasms, radiation lowers lymphocyte counts, weakens immune activation, and recruits suppressive myeloid cells impairing immune responses. Tumor environments treated with radiation experience long-term immunosuppression, reducing immunotherapy effectiveness and contributing to recurrence.
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