We investigated whether exposure to intermediate frequency magnetic fields (IF MFs) could induce or enhance genomic instability in primary astrocytes. Rat primary astrocytes were exposed to vertical or horizontal 7.5 kHz, 300 μT MF for 24 h. To study possible combined effects with known genotoxic agents, the cells were exposed for 3 h to menadione or methyl methanesulfonate after the MF treatment. Induced genomic instability was evaluated 36 days after exposures using the Comet assay and flow cytometric scoring of micronuclei. Exposure to 7.5 kHz, 300 μT MF did not induce genomic instability alone or in combination with chemicals in measurements performed several cell generations after exposure.
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http://dx.doi.org/10.1016/j.envres.2019.03.033 | DOI Listing |
Nat Genet
January 2025
Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
Understanding the molecular landscape of nonmuscle-invasive bladder cancer (NMIBC) is essential to improve risk assessment and treatment regimens. We performed a comprehensive genomic analysis of patients with NMIBC using whole-exome sequencing (n = 438), shallow whole-genome sequencing (n = 362) and total RNA sequencing (n = 414). A large genomic variation within NMIBC was observed and correlated with different molecular subtypes.
View Article and Find Full Text PDFCell Death Dis
January 2025
Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
Aging of the brain vasculature plays a key role in the development of neurovascular and neurodegenerative diseases, thereby contributing to cognitive impairment. Among other factors, DNA damage strongly promotes cellular aging, however, the role of genomic instability in brain endothelial cells (EC) and its potential effect on brain homeostasis is still largely unclear. We here investigated how endothelial aging impacts blood-brain barrier (BBB) function by using excision repair cross complementation group 1 (ERCC1)-deficient human brain ECs and an EC-specific Ercc1 knock out (EC-KO) mouse model.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of Michigan Medical School, Ann Arbor, MI, USA.
Background: The transfer of mitochondrial DNA into the nuclear genomes of eukaryotes (Numts) has been linked to lifespan in non-human species and recently demonstrated to occur in rare instances from one human generation to the next.
Method: Here we investigated numtogenesis dynamics in humans in two ways. First, we quantified Numts in 1,187 post-mortem brain and blood samples from different individuals.
Cancer Immunol Immunother
January 2025
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China.
Microsatellite stable (MSS) colorectal cancer (CRC) is a subtype of CRC that generally exhibits resistance to immunotherapy, particularly immune checkpoint inhibitors such as PD-1 blockade. This study investigates the effects and underlying mechanisms of combining PD-1 blockade with IDO1 inhibition in MSS CRC. Bioinformatics analyses of TCGA-COAD and TCGA-READ cohorts revealed significantly elevated IDO1 expression in CRC tumors, correlating with tumor mutation burden across TCGA datasets.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Background: Studies of the genetics of Alzheimer's disease (AD) have largely focused on single nucleotide variants and short insertions/deletions. However, much of the disease heritability has yet to be uncovered, suggesting that other forms of genetic variation promote substantial portions of genetic risk. Uncovering the genetic basis of AD can lead to new disease biomarkers and delineate disease mechanisms.
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