The impact of magnetic particulate matter (mPM) pollution as a contributing factor for development of childhood cancer: an in vitro and in vivo molecular and cellular analysis.

01 November 2021 → 31 October 2022
Funding by bilateral agreement (private and foundations)
Research disciplines
  • Medical and health sciences
    • Cancer biology
    • Cancer biology
fine dust cancer Pediatric DNA damage Inflammation
Project description

Pediatric cancer is rare, yet it is the second leading cause of death in children. The causes of childhood cancer are not yet fully known, but it is believed that both genetic and environmental factors play a role. Recently it became clear that 10% of new diagnoses of childhood cancer can be explained by an underlying genetic predisposition. In addition, environmental factors were also investigated, including high doses of ionizing radiation, prior chemotherapy and exposure to infections and pesticides.

Pollution, and more specifically particulate matter, is the largest environmental cause of disease in the world and is estimated to be responsible for 16% of all deaths worldwide. Particulate matter is released directly into the atmosphere and is mainly produced by combustion and mechanical processes and comes from agriculture, traffic, industry, mining activities or other similar activities. Children are particularly sensitive to this pollution, which is explained by the fact that their metabolic pathways are still immature, resulting in the inability to rapidly detoxify and excrete toxic pollutants. Their delicate developmental processes can be easily disrupted by very low doses of toxic components. Although some studies have shown a link between particulate matter and the development of cancer in children, no functional insights have been obtained into how particulate matter could contribute to the development of cancer in children.

In this proposal, magnetic particulate matter isolated from different hotspots in Flanders (and thus representing industrial and combustion-related activity from certain areas in Flanders) will be investigated for its cellular behavioral and molecular impact on cancer development. More specifically, we will investigate in vitro the impact of particulate matter on gene expression, DNA damage and inflammatory responses in different cell line models. In addition, the in vivo impact will be modeled using the TEL-AML1 fusion-positive B6.129S1-Etv6tm1 (RUNX1) Haho/J pre-leukemic mouse model, which represents the most common type of pediatric leukemia. These data will be integrated with epidemiological and environmental data (not part of this proposal).