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Updated: Jul 17, 2026

Quantification of three DNA Lesions by Mass Spectrometry and Assessment of Their Levels in Tissues of Mice Exposed to Ambient Fine Particulate Matter
Published on: May 29, 2019
Modulation of oxidative DNA damage repair by the diet, inflammation and neoplastic transformation
B Tudek1, M Swoboda, P Kowalczyk
1Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland. tudek@ibb.waw.pl
Abstract:
Oxidative DNA damage and DNA repair may mediate several cellular processes, like replication and transcription, mutagenesis and apoptosis and thus may be important for the organism development as well as its pathogenesis, including cancer. Activity of DNA repair enzymes can depend on many factors, such as gene polymorphism, mRNA and protein level, as well as enzymes activation and inhibition. Modulation of base excision repair pathway eliminating from DNA oxidatively formed lesions may be caused by the diet, inflammation and neoplastic transformation. Reactive oxygen species and some diet components induce transcription of several Base Excision Repair enzymes, e.g. major human AP-endonuclease, (APE1) and 8-oxoG-DNA glycosylase (OGG1). The carcinogenic process in human lung decreases repair activity for 8-oxoGin transcription independent manner, but increases repair activity of epsilon A and epsilon C, as measured in tumors and unchanged lung tissues of lung cancer patients. Thus, modulation of repair enzymes activities may be a cell response on their way to differentiation ot neoplastic transformation.
Insights
DNA repair pathways are crucial for cellular processes and organism development, with their activity influenced by various factors. Cancer development can alter DNA repair enzyme activity, highlighting its role in pathogenesis.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Oxidative DNA damage and repair are integral to cellular functions like replication, transcription, mutagenesis, and apoptosis.
- DNA repair enzyme activity is influenced by gene polymorphism, expression levels, and post-translational modifications.
- The base excision repair (BER) pathway removes oxidative DNA lesions and can be modulated by diet, inflammation, and neoplastic transformation.
Purpose of the Study:
- To investigate the role of oxidative DNA damage and repair in cellular processes and pathogenesis, particularly cancer.
- To explore the factors influencing DNA repair enzyme activity.
- To examine the modulation of BER pathway enzymes in the context of lung cancer.
Main Methods:
- Analysis of cellular processes mediated by oxidative DNA damage and repair.
- Assessment of factors affecting DNA repair enzyme activity, including gene polymorphism and expression.
- Evaluation of Base Excision Repair (BER) pathway modulation in response to diet, inflammation, and neoplastic transformation.
- Measurement of repair activity for specific lesions (e.g., 8-oxoG, epsilon A, epsilon C) in lung cancer tissues and adjacent normal tissues.
Main Results:
- Oxidative DNA damage and repair are implicated in organism development and pathogenesis, including cancer.
- Factors such as gene polymorphism, mRNA/protein levels, and enzyme activation/inhibition affect DNA repair enzyme activity.
- Diet and inflammation can modulate the BER pathway, influencing the removal of oxidative DNA lesions.
- Carcinogenesis in human lung alters the repair activity of specific BER enzymes, with decreased activity for 8-oxoG and increased activity for epsilon A and epsilon C in tumors.
Conclusions:
- Modulation of DNA repair enzyme activities represents a cellular response during differentiation and neoplastic transformation.
- Understanding these modulations is critical for comprehending cancer development and potentially for therapeutic strategies.
- The differential regulation of BER enzymes in lung cancer suggests a complex interplay between DNA repair and tumorigenesis.
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