Development of computational model for cell dose and DNA damage quantification of multicellular system

Photosensitized one-electron oxidation of DNA has attracted much interest because it causes oxidative damage which leads to mutation, and because it is involved in the basic mechanism of photodynamic therapy. In the present article, we describe the mechanistic study of photosensitized DNA damage, especially addressing the kinetics of hole transfer by adenine(A)-hopping and its effect on the DNA damage. The combination of the transient absorption measurement and DNA damage quantification by high-performance liquid chromatography clearly demonstrate that the yield of the DNA damage correlates well with the lifetime of the charge-separated state caused by A-hopping, showing that hole transfer helps DNA damage. These findings led us to propose a new method to accomplish the efficient DNA damage using a combination of two-color, two-laser irradiation.

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LORD-Q: a long-run real-time PCR-based DNA-damage quantification method for nuclear and mitochondrial genome analysis

Nucleic Acids Research ◽

10.1093/nar/gkt1349 ◽

2013 ◽

Vol 42 (6) ◽

pp. e41-e41 ◽

Cited By ~ 22

Author(s):

Simon Lehle ◽

Dominic G. Hildebrand ◽

Britta Merz ◽

Peter N. Malak ◽

Michael S. Becker ◽

...

Keyword(s):

Dna Damage ◽

Mitochondrial Genome ◽

Real Time ◽

Genome Analysis ◽

Real Time Pcr ◽

Quantification Method ◽

Damage Quantification ◽

Long Run

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Simultaneous quantification of DNA damage and mitochondrial copy number by long-run DNA-damage quantification (LORD-Q)

Oncotarget ◽

10.18632/oncotarget.20112 ◽

2017 ◽

Vol 8 (68) ◽

pp. 112417-112425 ◽

Cited By ~ 1

Author(s):

Benjamin Dannenmann ◽

Simon Lehle ◽

Sebastian Lorscheid ◽

Stephan M. Huber ◽

Frank Essmann ◽

...

Keyword(s):

Dna Damage ◽

Copy Number ◽

Simultaneous Quantification ◽

Damage Quantification ◽

Long Run ◽

Mitochondrial Copy Number

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Experimental design, validation and computational modeling uncover DNA damage sensing by DNA-PK and ATM

Molecular BioSystems ◽

10.1039/c4mb00093e ◽

2014 ◽

Vol 10 (7) ◽

pp. 1978-1986 ◽

Cited By ~ 5

Author(s):

R. J. Flassig ◽

G. Maubach ◽

C. Täger ◽

K. Sundmacher ◽

M. Naumann

Keyword(s):

Dna Damage ◽

Experimental Design ◽

Computational Modeling ◽

Computational Model ◽

Ionizing Irradiation ◽

Design Validation ◽

Damage Sensing

A computational model predicts biphasic activation of γH2AX by DNA-PKcs and ATM-P upon DNA damage, which is induced by ionizing irradiation (IR).

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Micropatterned comet assay enables high throughput and sensitive DNA damage quantification

Mutagenesis ◽

10.1093/mutage/geu063 ◽

2014 ◽

Vol 30 (1) ◽

pp. 11-19 ◽

Cited By ~ 22

Author(s):

J. Ge ◽

D. N. Chow ◽

J. L. Fessler ◽

D. M. Weingeist ◽

D. K. Wood ◽

...

Keyword(s):

Dna Damage ◽

Comet Assay ◽

High Throughput ◽

Damage Quantification

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Computational Model of the Modulation of Gene Expression Following DNA Damage

Radiation Protection Dosimetry ◽

10.1093/oxfordjournals.rpd.a006846 ◽

2002 ◽

Vol 99 (1) ◽

pp. 85-89 ◽

Cited By ~ 11

Author(s):

F. A. Cucinotta ◽

J. F. Dicello ◽

H. Nikjoo ◽

R. Cherubini

Keyword(s):

Gene Expression ◽

Dna Damage ◽

Computational Model ◽

Modulation Of Gene Expression

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Computational Model of G2-M DNA Damage Checkpoint Regulation in Normal and p53-null Cancer Cells

10.1101/2020.06.17.158246 ◽

2020 ◽

Author(s):

Yongwoon Jung ◽

Pavel Kraikivski

Keyword(s):

Cell Cycle ◽

Dna Damage ◽

Computational Model ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Cell Cycle Progression ◽

Dna Damage Checkpoint ◽

Cycle Progression ◽

Normal Cells ◽

Cycle Arrest

AbstractCancer and normal cells can respond differently to the same stressful conditions. Their dynamic responses under normal and stressful conditions are governed by complex molecular regulatory networks. We developed a computational model of G2-M DNA damage checkpoint regulation to study normal and cancer cell cycle progression under normal and stressful conditions. Our model is successful in explaining cancer cell cycle arrest in conditions when some cell cycle and DNA damage checkpoint regulators are inhibited, whereas the same conditions only delay entry into mitosis in normal cells. We use the model to explain known phenotypes of gene deletion mutants and predict phenotypes of yet uncharacterized mutants in normal and cancer cells. We also use sensitive analyses to identify the ranges of model parameter values that lead to the cell cycle arrest in cancer cells. Our results can be used to predict the effect of a potential treatment on cell cycle progression of normal and cancer cells.

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Augmented Microscopy for DNA Damage Quantification: A Machine Learning Tool for Environmental, Medical and Health Sciences

Volume 9: 15th IEEE/ASME International Conference on Mechatronic and Embedded Systems and Applications ◽

10.1115/detc2019-97902 ◽

2019 ◽

Cited By ~ 1

Author(s):

Michele Bernardini ◽

Alessandro Ferri ◽

Lucia Migliorelli ◽

Sara Moccia ◽

Luca Romeo ◽

...

Keyword(s):

Machine Learning ◽

Dna Damage ◽

Comet Assay ◽

Computation Time ◽

Health Sciences ◽

Experimental Results ◽

Research Areas ◽

Damage Quantification ◽

Scoring Accuracy ◽

Machine Learning Tool

Abstract The Comet Assay is a well-known procedure employed to investigate the DNA damage and can be applied to several research areas such as environmental, medical and health sciences. User dependency and computation time effort represent some of the major drawbacks of the Comet Assay. Starting from this motivation, we applied a Machine Learning (ML) tool for discriminating DNA damage using a standard hand-crafted feature set. The experimental results demonstrate how the ML tool is able to objectively replicate human experts scoring (accuracy detection up to 92%) by solving the related binary task (i.e., controls vs damaged comets).

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