Department of Pharmacology & Toxicology

DNA damage and repair Modulation of DNA damage and repair by Inflammation

Chronic inflammation is considered to be a risk factor for the development of epithelial cell derived malignancies. However the underlying processes have not yet been fully defined at the biochemical and molecular level. Within the lung, many inflammatory agents may play a part in accelerating carcinogenesis, including inhaled combustion derived particles, such as cigarette smoke. One of the most accepted explanations for these carcinogenic effects is the ability of combustion derived particles to transport chemical carcinogens, such as Polycyclic Aromatic Hydrocarbons (PAH), into the lungs. Another characteristic of these particles is however that they elicit an influx of polymorphonuclear neutrophils (PMN) into the airways upon inhalation, which is most evident in smokers who developed chronic obstructive pulmonary disease (COPD). The interesting thing is that smokers who have COPD appear to run an increased risk of developing lung cancer (up to 10 fold), suggesting a significant role of the ongoing neutrophil inflammation in this carcinogenic response. In the past, neutrophils have been implicated in (pulmonary) carcinogenicity by their genotoxic capacity through the release of mutagenic reactive oxygen species (ROS), which induce oxidative DNA damage, as well as by promoting the metabolic activation of environmental chemical carcinogens via the enzyme myeloperoxidase (MPO), resulting in premutagenic DNA adducts. This project focuses more specifically on the effect of neutrophils and myeloperoxidase on the nucleotide excision repair processes involved in the removal of such premutagenic DNA lesions (in vitro & in vivo), thereby contributing to a further understanding of the mechanisms underlying the association between inflammation and cancer development. We also showed that inflammatory cells could inhibit DNA repair capacities in co-cultured lung-epithelial cells. This effect was dependent on myeloperoxidase-catalysed production of hypochlorous acid and could further increase genetic instability.

We propose that these mechanisms provide an explanation for the association between chronic pulmonary inflammatory diseases (e.g. COPD) or inflammation in the liver (NASH) and cancer development.

Associated Staff

Roger Godschalk
Assistant Professor

​Dr. Roger Godschalk graduated in Biological Health Sciences in 1995 at the Maastricht University (The Netherlands). He specialised in genetic toxicol more ...

Frederik-Jan van Schooten
Professor, Head of the department

​Prof. van Schooten studied biology at the Free University of Amsterdam, The Netherlands, where he specialised in immunology, molecular microbiology a more ...

Agnes Boots
Assistant Professor

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Geja hageman
Assistant Professor

​Dr. Hageman studied agricultural sciences at Wageningen University. She graduated in 1985, having specialized in human nutrition and food science. Sh more ...

Charlotte Pauwels
PhD Student

​Charlotte Pauwels was born on April 6th 1990 in Duffel, Belgium. In 2008, she started her study Biomedical Sciences at the Radboud University, Nijmeg more ...

Carmen Veith
PhD Student

​Carmen Veith was born on February 3rd 1990 in Buehl, Germany. In 2009 she started the Bachelor program Molecular Life Sciences at Maastricht Universi more ...

Nuan Ping Cheah
Former Staff

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Quan Shi
PhD Student

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Daniëlle Pachen
Technician

​Daniëlle Pachen studied at the technical school for chemistry in Heerlen, and she is specialised in analytical an instrumental techniques. From 1991 more ...

Lou Maas
Technician

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Ellen Higgs
PhD Student

Ellen Higgs graduated from Keele University in 2014 after studying Biochemistry and Forensic Science. She then enrolled in a Research Masters in Cance more ...