Mechanistic studies of in vitro cytotoxicity of poly(amidoamine) dendrimers in mammalian cells.

Toxicol Appl Pharmacol

Radiation and Environmental Science Centre, Focas Research Institute, Dublin, Institute of Technology, Kevin Street, Dublin 8, Ireland.

Published: November 2010

Poly(amidoamine) (PAMAM) dendrimer nanoparticles have been demonstrated to elicit a well defined cytotoxicological response from mammalian cell lines, the response increasing systematically with dendrimer generation and number of surface amino groups. In this work, using generation G4, G5, and G6 dendrimers, this systematic response is furthermore demonstrated for the generation of reactive oxygen species, lysosomal activity, and the onset of apoptosis and levels of DNA damage. The results are consistent with a pathway of localisation of PAMAM dendrimers in the mitochondria leading to ROS production causing oxidative stress, apoptosis and DNA damage. ROS production is co-located in the mitochondria, and both generated levels and timescales are systematically generation dependent (G4

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.taap.2010.08.016DOI Listing

Publication Analysis

Top Keywords

dna damage
8
ros production
8
mechanistic studies
4
studies vitro
4
vitro cytotoxicity
4
cytotoxicity polyamidoamine
4
polyamidoamine dendrimers
4
dendrimers mammalian
4
mammalian cells
4
cells polyamidoamine
4

Similar Publications

Sperm motility is the prime functional attribute for semen quality and fertility of the bull. However, the bull's age directly affects the semen quality, and the bull's fertility and productive life decline with age. Even though research on age has been conducted in the past, it is still unclear how old a bull should be maintained at artificial insemination centers.

View Article and Find Full Text PDF

Quantifying DNA Lesions and Circulating Free DNA: Diagnostic Marker for Electropathology and Clinical Stage of AF.

JACC Clin Electrophysiol

December 2024

Physiology, Amsterdam Cardiovascular Sciences, Heart Failure, and Arrhythmias, Amsterdam University Medical Center, location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands. Electronic address:

Background: Atrial fibrillation (AF) persistence is associated with molecular remodeling that fuels electrical conduction abnormalities in atrial tissue. Previous research revealed DNA damage as a molecular driver of AF.

Objectives: This study sought to explore the diagnostic value of DNA damage in atrial tissue and blood samples as an indicator of the prevalence of electrical conduction abnormalities and stage of AF.

View Article and Find Full Text PDF

Extensive homologous recombination safeguards oocyte genome integrity in mammals.

Nucleic Acids Res

January 2025

MOE Key Laboratory of Biosystems Homeostasis and Protection, College of Life Sciences, Zhejiang University, No.866 Yuhangtang Road, 310058, Hangzhou, China.

Meiosis in mammalian oocytes is interrupted by a prolonged arrest at the germinal vesicle stage, during which oocytes have to repair DNA lesions to ensure genome integrity or otherwise undergo apoptosis. The FIRRM/FLIP-FIGNL1 complex dissociates RAD51 from the joint DNA molecules in both homologous recombination (HR) and DNA replication. However, as a type of non-meiotic, non-replicative cells, whether this RAD51-dismantling mechanism regulates genome integrity in oocytes remains elusive.

View Article and Find Full Text PDF

GDBr: genomic signature interpretation tool for DNA double-strand break repair mechanisms.

Nucleic Acids Res

January 2025

Department of Convergent Bioscience and Informatics, College of Bioscience and Biotechnology, Chungnam National University, 99, Daehak-ro, Yuseong-gu, Daejeon 34134, Republic of Korea.

Large genetic variants can be generated via homologous recombination (HR), such as polymerase theta-mediated end joining (TMEJ) or single-strand annealing (SSA). Given that these HR-based mechanisms leave specific genomic signatures, we developed GDBr, a genomic signature interpretation tool for DNA double-strand break repair mechanisms using high-quality genome assemblies. We applied GDBr to a draft human pangenome reference.

View Article and Find Full Text PDF

Altered DNA dynamics at lesion sites are implicated in how DNA repair proteins sense damage within genomic DNA. Using laser temperature-jump (T-jump) spectroscopy combined with cytosine-analog Förster Resonance Energy Transfer (FRET) probes that sense local DNA conformations, we measured the intrinsic dynamics of DNA containing 3 base-pair mismatches recognized in vitro by Rad4 (yeast ortholog of XPC). Rad4/XPC recognizes diverse lesions from environmental mutagens and initiates nucleotide excision repair.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!